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  1. Genetic counseling services and development of training programs in Malaysia
    Lee JM, Thong MK
    J Genet Couns, 2013 Dec;22(6):911-6.
    PMID: 23615969 DOI: 10.1007/s10897-013-9589-z
    Genetic counseling service is urgently required in developing countries. In Malaysia, the first medical genetic service was introduced in 1994 at one of the main teaching hospitals in Kuala Lumpur. Two decades later, the medical genetic services have improved with the availability of genetic counseling, genetic testing and diagnosis, for both paediatric conditions and adult-onset inherited conditions, at four main centers of medical genetic services in Malaysia. Prenatal diagnosis services and assisted reproductive technologies are available at tertiary centres and private medical facilities. Positive developments include governmental recognition of Clinical Genetics as a subspecialty, increased funding for genetics services, development of medical ethics guidelines, and establishment of support groups. However, the country lacked qualified genetic counselors. Proposals were presented to policy-makers to develop genetic counseling courses. Challenges encountered included limited resources and public awareness, ethical dilemmas such as religious and social issues and inadequate genetic health professionals especially genetic counselors.
  2. Disturbance gradient and mosquito diversity pattern in areas surrounding Chini Lake - the second largest freshwater lake in Peninsular Malaysia
    Pathy TS, Lee JM, Yek SH
    Biodivers Data J, 2022;10:e83800.
    PMID: 36761566 DOI: 10.3897/BDJ.10.e83800
    Malaysia is a tropical country that has consistently been facing a prevalent threat of mosquito-borne diseases. Amongst the plethora of diseases, the most common mosquito-borne disease in the country is dengue fever, transmitted by Aedes spp. mosquitoes. This study aims to examine the effects of human activity associated with different land use on mosquito population composition and diversity. Our study site is Chini Lake, a naturally occurring lake and the second-largest freshwater body in Malaysia. The areas surrounding the Lake have been subjected to various human activities, such as economic development and conversion into rubber plantations, while some areas remain pristine, making Chini Lake an ideal location to examine the gradient of human disturbances on mosquito composition and diversity. We sampled adult mosquitoes and larvae across a range of sites with different levels of human disturbance. As expected, in areas with high disturbance scores, the species richness of adult and larval mosquitoes were reduced while the abundance was higher. The results also revealed minimal overlap between species captured for adult and larval samplings, suggesting that land-use changes affect both life stages differently. Different resource requirements of adult and larval mosquitoes likely led to the observed diversity pattern in this small survey. We suggest future work to look into how habitat heterogeneity affects both life stages and sexes of mosquito diversity patterns and distribution.
  3. Characterization of the Aedes albopictus (Diptera: Culicidae) holobiome: bacterial composition across land use type and mosquito sex in Malaysia
    Lee JM, Yek SH, Wilson RF, Rahman S
    Acta Trop, 2020 Dec;212:105683.
    PMID: 32888935 DOI: 10.1016/j.actatropica.2020.105683
    Understanding the diversity and dynamics of the microbiota within the mosquito holobiome is of great importance to apprehend how the microbiota modulates various complex processes and interactions. This study examined the bacterial composition of Aedes albopictus across land use type and mosquito sex in the state of Selangor, Malaysia using 16S rRNA sequencing. The bacterial community structure in mosquitoes was found to be influenced by land use type and mosquito sex, with the environment and mosquito diet respectively identified to be the most likely sources of microbes. We found that approximately 70% of the microbiota samples were dominated by Wolbachia and removing Wolbachia from analyses revealed the relatively even composition of the remaining bacterial microbiota. Furthermore, microbial interaction network analysis highlighted the prevalence of co-exclusionary patterns in all networks regardless of land use and mosquito sex, with Wolbachia exhibiting co-exclusionary interactions with other residential bacteria such as Xanthomonas, Xenophilus and Zymobacter.
  4. Human Activities Attract Harmful Mosquitoes in a Tropical Urban Landscape
    Lee JM, Wasserman RJ, Gan JY, Wilson RF, Rahman S, Yek SH
    Ecohealth, 2020 03;17(1):52-63.
    PMID: 31786667 DOI: 10.1007/s10393-019-01457-9
    Knowledge of the interrelationship of mosquito communities and land use changes is of paramount importance to understand the potential risk of mosquito disease transmission. This study examined the effects of land use types in urban, peri-urban and natural landscapes on mosquito community structure to test whether the urban landscape is implicated in increased prevalence of potentially harmful mosquitoes. Three land use types (park, farm, and forest nested in urban, peri-urban and natural landscapes, respectively) in Klang Valley, Malaysia, were surveyed for mosquito larval habitat, mosquito abundance and diversity. We found that the nature of human activities in land use types can increase artificial larval habitats, supporting container-breeding vector specialists such as Aedes albopictus, a dengue vector. In addition, we observed a pattern of lower mosquito richness but higher mosquito abundance, characterised by the high prevalence of Ae. albopictus in the urban landscape. This was also reflected in the mosquito community structure whereby urban and peri-urban landscapes were composed of mainly vector species compared to a more diverse mosquito composition in natural landscape. This study suggested that good environmental management practices in the tropical urban landscape are of key importance for effective mosquito-borne disease management.
  5. Fulltext Raising cigarette excise tax to reduce consumption in low-and middle-income countries of the Asia-Pacific region:a simulation of the anticipated health and taxation revenues impacts
    Ho LM, Schafferer C, Lee JM, Yeh CY, Hsieh CJ
    BMC Public Health, 2018 Oct 19;18(1):1187.
    PMID: 30340557 DOI: 10.1186/s12889-018-6096-z
    BACKGROUND: According to the World Health Organization (WHO), 80% of the world's smokers live in low- and middle-income countries. Moreover, more than half of the world's smoking-addicted population resides in the Asia-Pacific region. The reduction of tobacco consumption has thus become one of the major social policies in the region. This study investigates the effects of price increases on cigarette consumption, tobacco tax revenues and reduction in smoking-caused mortality in 22 low-income as well as middle-income countries in the Asia-Pacific region.

    METHODS: Using panel data from the 1999-2015 Euromonitor International, the World Bank and the World Health Organization, we applied fixed effects regression models of panel data to estimate the elasticity of cigarette prices and to simulate the effect of price fluctuations.

    RESULTS: Cigarette price elasticity was the highest for countries with a per capita Gross National Income (GNI) above US$6000 (China and Malaysia), and considerably higher for other economies in the region. The administered simulation shows that with an average annual cigarette price increase of 9.51%, the average annual cigarette consumption would decrease by 3.56%, and the average annual tobacco tax revenue would increase by 16.20%. The number of averted smoking-attributable deaths (SADs) would be the highest in China, followed by Indonesia and India. In total, over 17.96 million lives could be saved by tax increases.

    CONCLUSION: Excise tax increases have a significant effect on the reduction of smoking prevalence and the number of averted smoking-attributable deaths. Middle- and upper-middle income countries would be most affected by high-taxation policies.

  6. Fulltext Lead isotope exchange between dissolved and fluvial particulate matter: a laboratory study from the Johor River estuary
    Chen M, Boyle EA, Lee JM, Nurhati I, Zurbrick C, Switzer AD, et al.
    Philos Trans A Math Phys Eng Sci, 2016 11 28;374(2081).
    PMID: 29035266 DOI: 10.1098/rsta.2016.0054
    Atmospheric aerosols are the dominant source of Pb to the modern marine environment, and as a result, in most regions of the ocean the Pb isotopic composition of dissolved Pb in the surface ocean (and in corals) matches that of the regional aerosols. In the Singapore Strait, however, there is a large offset between seawater dissolved and coral Pb isotopes and that of the regional aerosols. We propose that this difference results from isotope exchange between dissolved Pb supplied by anthropogenic aerosol deposition and adsorbed natural crustal Pb on weathered particles delivered to the ocean by coastal rivers. To investigate this issue, Pb isotope exchange was assessed through a closed-system exchange experiment using estuarine waters collected at the Johor River mouth (which discharges to the Singapore Strait). During the experiment, a known amount of dissolved Pb with the isotopic composition of NBS-981 (206Pb/207Pb = 1.093) was spiked into the unfiltered Johor water (dissolved and particulate 206Pb/207Pb = 1.199) and the changing isotopic composition of the dissolved Pb was monitored. The mixing ratio of the estuarine and spike Pb should have produced a dissolved 206Pb/207Pb isotopic composition of 1.161, but within a week, the 206Pb/207Pb in the water increased to 1.190 and continued to increase to 1.197 during the next two months without significant changes of the dissolved Pb concentration. The kinetics of isotope exchange was assessed using a simple Kd model, which assumes multiple sub-reservoirs within the particulate matter with different exchange rate constants. The Kd model reproduced 56% of the observed Pb isotope variance. Both the closed-system experiment and field measurements imply that isotope exchange can be an important mechanism for controlling Pb and Pb isotopes in coastal waters. A similar process may occur for other trace elements.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.
  7. Limited Effect of Ground Floor Fogging on Mosquito Distribution in High-Rise Condominia
    Lee JM, Wasserman RJ, Wilson RF, Cuthbert RN, Rahman S, Yek SH
    Ecohealth, 2023 Mar;20(1):65-73.
    PMID: 37129695 DOI: 10.1007/s10393-023-01629-8
    Fogging with insecticides is one of the main control measures for adult mosquito populations employed in countries that are affected by dengue. In many such countries, urban communities are increasingly characterised by high-density residence in high-rise condominia. Although fogging is typically applied at the ground level, its efficacy in three-dimensional urban environments is poorly understood. Here, we investigated the effect of fogging on vector mosquito distribution and abundance in high-rise condominia by conducting a before-after fogging survey. We showed that although mosquitoes were significantly concentrated at the lower levels in high-rise condominia, they were found throughout the three-dimensional environments. Fogging did not significantly alter this distribution or abundance pattern across any floor level. Thus, any fogging effect was short-lived as mosquito populations recovered within a few days before the subsequent scheduled treatment. In addition, increasing fogging frequency within practicable limits did not prolong the intended control effect. As urban mosquitoes are increasingly insusceptible to fogging due to insecticide resistance and vertical avoidance, this study demonstrates the need to implement other mosquito control strategies for high-rise condominia to manage mosquito populations.
  8. Fulltext Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review
    Chong LC, Gandhi G, Lee JM, Yeo WWY, Choi SB
    Int J Mol Sci, 2021 Aug 20;22(16).
    PMID: 34445667 DOI: 10.3390/ijms22168962
    Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.
  9. Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore
    Yeo KK, Tai BC, Heng D, Lee JM, Ma S, Hughes K, et al.
    Diabetologia, 2006 Dec;49(12):2866-73.
    PMID: 17021918 DOI: 10.1007/s00125-006-0469-z
    AIMS/HYPOTHESIS: The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups.

    METHODS: Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression.

    RESULTS: Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk.

    CONCLUSIONS/INTERPRETATION: Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.
  10. Fulltext Effect of an intensive patient educational programme on the quality of bowel preparation for colonoscopy: a single-blind randomised controlled trial
    Janahiraman S, Tay CY, Lee JM, Lim WL, Khiew CH, Ishak I, et al.
    BMJ Open Gastroenterol, 2020 05;7(1).
    PMID: 32371502 DOI: 10.1136/bmjgast-2020-000376
    OBJECTIVE: Preprocedural bowel preparation is necessary for optimal colonoscopy visualisation. However, it is challenging to achieve high-quality bowel preparation among patients scheduled for colonoscopy. This study aims to evaluate the impact of an intensive patient educational programme on the quality of bowel preparation.

    DESIGN: An accessor-blinded randomised controlled trial was carried out at the outpatient surgical clinic of a tertiary hospital. Patients were randomly assigned to the control group (received standard written and verbal instructions) or the experimental group (received an intensive and structured educational programme). All subjects completed a questionnaire before colonoscopy to assess their compliance, acceptability, and tolerability towards bowel preparation regime. Quality of bowel preparation was determined using the Boston Bowel Preparation Scale (BBPS).

    RESULTS: A total of 300 subjects who fulfilled the inclusion criteria were recruited. The experimental group had a significantly higher proportion of good quality bowel preparation than the control group (98.7% vs 52.3%, p<0.001). The median total BBPS score was also significantly higher in the experimental group (8 vs 5, p<0.001). Factors associated with good quality of bowel preparation included educational programme (OR: 22.79, 95% CI: 4.23 to 122.85, p<0.001), compliance to bowel cleansing agent (OR: 24.98, 95% CI 3.12 to 199.71, p<0.001), very difficult acceptability of preparation (OR: 0.11, 95% CI 0.03 to 0.38, p<0.001), tolerability towards bowel preparation (OR: 4.98, 95% CI 1.44 to 17.20, p<0.011) and hypomotility drugs (OR: 3.03, 95% CI 0.12 to 0.91, p<0.05).

    CONCLUSION: An intensive patient educational programme can significantly improve the quality of bowel preparation for colonoscopy.

  11. Genetic counseling/consultation in South-East Asia: a report from the workshop at the 10th Asia pacific conference on human genetics
    Zayts O, Sarangi S, Thong MK, Chung BH, Lo IF, Kan AS, et al.
    J Genet Couns, 2013 Dec;22(6):917-24.
    PMID: 24048708 DOI: 10.1007/s10897-013-9646-7
    This paper reports on the workshop 'Genetic Counseling/Consultations in South-East Asia' at the 10(th) Asia Pacific Conference on Human Genetics in Kuala Lumpur, Malaysia, in December 2012. The workshop brought together professionals and language/communication scholars from South-East Asia, and the UK. The workshop aimed at addressing culture- and context-specific genetic counseling/consultation practices in South-East Asia. As a way of contextualizing genetic counseling/consultation in South-East Asia, we first offer an overview of communication-oriented research generally, drawing attention to consultation and counseling as part of a communicative continuum with distinctive interactional features. We then provide examples of genetic counseling/consultation research in Hong Kong. As other countries in South-East Asia have not yet embarked on communication-oriented empirical research, we report on the current practices of genetic counseling/consultation in these countries in order to identify similarities and differences as well as key obstacles that could be addressed through future research. Three issues emerged as 'problematic': language, religion and culture. We suggest that communication-oriented research can provide a starting point for evidence-based reflections on how to incorporate a counseling mentality in genetic consultation. To conclude, we discuss the need for creating a platform for targeted training of genetic counselors based on communication-oriented research findings.
  12. Fulltext Provisional drug-coated balloon treatment guided by physiology on de novo coronary lesion
    Shin ES, Bang LH, Jun EJ, Her AY, Chung JH, Garg S, et al.
    Cardiol J, 2021;28(4):615-622.
    PMID: 32789835 DOI: 10.5603/CJ.a2020.0105
    Although drug-eluting stents (DES) have become the mainstay of percutaneous coronary intervention, late and very late stent thrombosis remains a concern. Drug-coated balloons (DCB) have the advantage of preserving the anti-restenotic benefits of DES while minimizing potential long-term safety concerns. Currently the two methods to ensure successful DCB treatment of a stenotic lesion are angiography or physiology-guided DCB application. This review will evaluate these two methods based on previous evidence and make suggestions on how to perform DCB treatment more efficiently and safely.
  13. Biological sex modifies aldosterone's secretion at a cellular level
    Gholami SK, Tay CS, Lee JM, Zagoren E, Maris SA, Wong JY, et al.
    J Endocrinol, 2021 11 24;252(1):1-13.
    PMID: 34643545 DOI: 10.1530/JOE-21-0126
    Inconsistencies have been reported on the effect of sex on aldosterone (ALDO) levels leading to clinical confusion. The reasons for these inconsistencies are uncertain but include estrogen and/or its receptor modulating target gene responses to mineralocorticoid receptor activation and ALDO secretagogues' levels. This study's goal was to determine whether ALDO's biosynthesis also differed by sex. Two approaches were used. First, plasma renin activity and aldosterone were measured in rats. Both were significantly higher in males. Secondly, using rat zona glomerulosa (ZG) cells, we assessed three ex vivo areas: (1) activity/levels of early steps in ALDO's biosynthesis (StAR and CYP11A1); (2) activity/levels of a late step (CYP11B2); and (3) the status of the mineralocorticoid receptor (MR)-mediated, ultrashort feedback loop. Females had higher expression of CYP11A1 and StAR and increased CYP11A1 activity (increased pregnenolone/corticosterone levels) but did not differ in CYP11B2 expression or activity (ALDO levels). Activating the ZG's MR (thereby activating the ultrashort feedback loop) reduced CYP11B2's activity similarly in both sexes. Exvivo, these molecular effects were accompanied, in females, by lower ALDO basally but higher ALDO with angiotensin II stimulation. In conclusion, we documented that not only was there a sex-mediated difference in the activity of ALDO's biosynthesis but also these differences at the molecular level help explain the variable reports on ALDO's circulating levels. Basally, both in vivo and ex vivo, males had higher ALDO levels, likely secondary to higher ALDO secretagogue levels. However, in response to acute stimulation, ALDO levels are higher in females because of the greater levels and/or activity of their StAR/CYP11A1.
  14. The appearance of a second genotype of Japanese encephalitis virus in the Australasian region
    Pyke AT, Williams DT, Nisbet DJ, van den Hurk AF, Taylor CT, Johansen CA, et al.
    Am J Trop Med Hyg, 2001 Dec;65(6):747-53.
    PMID: 11791969
    In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Culex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TS00 and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.
  15. Polypharmacy and potentially inappropriate medications among hospitalized older adults with COVID-19 in Malaysian tertiary hospitals
    Chang CT, Mohd Shariff SM, Abu Bakar NS, Ramzuzzaman NS, Lim CK, Lim EYJ, et al.
    J Pharm Policy Pract, 2023 Jan 12;16(1):2.
    PMID: 36635766 DOI: 10.1186/s40545-022-00504-1
    INTRODUCTION: Older adults are among the most vulnerable groups during the COVID-19 epidemic, contributing to a large proportion of COVID-19-related death. Medication review and reconciliation by pharmacist can help reduce the number of potentially inappropriate medications but these services were halted during COVID-19.

    AIM: To assess the prevalence and factors associated with inappropriate medicine use among older populations with COVID-19.

    METHODS: This was a cross-sectional, retrospective analysis of medications among hospitalized older adults with COVID-19. Potentially inappropriate medication use was categorized using the Beer's and STOPP criteria.

    RESULTS: Combining both criteria, 181 (32.7%) of the 553 patients were identified to have used at least one or more potentially inappropriate medication. A marginally higher number of inappropriate medications was documented using the Beers 2019 criteria (151 PIM in 124 patients) compared to STOPP criteria (133 PIMS in 104 patients). The long-term use of proton pump inhibitors (n = 68; 12.3%) and drugs which increases the risk of postural hypotension were the most commonly reported PIM (n = 41; 7.4%). Potentially inappropriate medication use was associated with previous history of hospital admission in the past 12 months (Odds ratio [OR]: 2.27; 95% CI 1.29-3.99) and higher number of discharge medications.

    CONCLUSIONS: Nearly, one in three older adults with COVID-19 had been prescribed a PIM, and the proportion of older adults with polypharmacy increased after discharge. This highlights the importance of having clinical pharmacist conducting medication reviews to identify PIMs and ensure medication appropriateness.

  16. International stroke genetics consortium recommendations for studies of genetics of stroke outcome and recovery
    Lindgren AG, Braun RG, Juhl Majersik J, Clatworthy P, Mainali S, Derdeyn CP, et al.
    Int J Stroke, 2021 Apr 26.
    PMID: 33739214 DOI: 10.1177/17474930211007288
    Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.
  17. Fulltext Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1
    Koo BK, Lee JM, Hwang D, Park S, Shiono Y, Yonetsu T, et al.
    JACC Asia, 2023 Oct;3(5):689-706.
    PMID: 38095005 DOI: 10.1016/j.jacasi.2023.07.003
    Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.
  18. Fulltext Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2
    Koo BK, Hwang D, Park S, Kuramitsu S, Yonetsu T, Kim CH, et al.
    JACC Asia, 2023 Dec;3(6):825-842.
    PMID: 38155788 DOI: 10.1016/j.jacasi.2023.07.004
    Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.
  19. Fulltext Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer
    Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, et al.
    Carcinogenesis, 2015 Nov;36(11):1341-53.
    PMID: 26424751 DOI: 10.1093/carcin/bgv138
    Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
  20. Fulltext Identification of six new susceptibility loci for invasive epithelial ovarian cancer
    Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, et al.
    Nat Genet, 2015 Feb;47(2):164-71.
    PMID: 25581431 DOI: 10.1038/ng.3185
    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
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