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Fulltext Interleukin 1β (+3954; -511) Genotype Polymorphism and its Association with Severe Chronic Generalized Periodontitis in the Malaysian Population

Arora S, Ramachandra SS, Abdullah F, Gundavarapu KC

Contemp Clin Dent, 2017 Jan-Mar;8(1):102-105.
PMID: 28566859 DOI: 10.4103/ccd.ccd_1177_16

INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in interleukin 1β (IL-1β) gene have been known to be associated with increased susceptibility to chronic periodontitis among various ethnic populations. SNPs are more commonly observed at loci + 3954 and - 511. The aim of this study was to evaluate the role of IL-1β gene polymorphism at loci +3954 and - 511, and its association with severe chronic generalized periodontitis among the ethnic Malay, Chinese, and Indians within the Malaysian population.

MATERIALS AND METHODS: Saliva samples from 120 subjects (60 cases and 60 controls) in the age group of 25-50 years were collected for isolation of genetic material using Norgen technique. Clinical attachment loss of ≥5 mm was considered as severe chronic generalized periodontitis. SNP's at loci +3954 and - 511 were identified and analyzed using Kompetitive Allele Specific Polymerase Chain Reaction Genotyping System (KASP™). Differences in the allele/genotype frequencies were assessed by Chi-square test (P < 0.05).

RESULTS: On the comparison between cases and controls of IL-1β genotype polymorphism (+3954 and - 511), the difference in the genotype frequencies was statistically insignificant in all the three ethnicities. The genotype frequency in both groups in all three ethnicities of the Malaysian population was similar.

CONCLUSION: IL-1β genotype polymorphism at +3954 and - 511 was found to be not associated with severe chronic generalized periodontitis among the three ethnicities in Malaysia. Studies with larger sample size should be done to confirm the findings of this study.

Matched MeSH terms: Gene Frequency
Fulltext Diagnostic Utility of Human Leukocyte Antigen B*15:02 Screening in Severe Carbamazepine Hypersensitivity Syndrome

Moutaouakkil Y, Adouani B, Cherrah Y, Lamsaouri J, Bousliman Y

Ann Indian Acad Neurol, 2019 10 25;22(4):377-383.
PMID: 31736555 DOI: 10.4103/aian.AIAN_492_18

Background: Despite many studies suggesting an association between human leukocyte antigen (HLA)-B*15:02 and carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions essentially toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), the evidence of association in different populations and the degree of association remain uncertain.
Materials and Methods: The primary analysis was based on population control studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratios (DOR), and areas under the summary receiver operating characteristic curve (AUC) were calculated.
Results: In 23 population control studies, HLA-B*15:02 was measured in 373 patients with CBZ-induced TEN/SJS and 3452 patients without CBZ-induced TEN/SJS. The pooled sensitivity, specificity, LR+, LR-, DOR, and AUC were 0.67 (95% confidence interval [CI] = 0.63-0.72), 0.98 (95% CI = 0.98-0.99), 19.73 (95% CI = 10.54-36.92), 0.34 (95% CI = 0.23-0.49), 71.38 (95% CI = 34.89-146.05), and 0.96 (95% CI = 0.92-0.98), respectively. Subgroup analyses for Han Chinese, Thai, and Malaysian populations yielded similar findings. Specifically, racial/ethnic subgroup analyses revealed similar findings with respect to DOR for Han Chinese (99.28; 95% CI = 22.20-443.88), Thai (61.01; 95% CI = 23.05-161.44), and Malaysian (30; 95% CI = 7.08-126.68) populations, which are similar to the pooled DOR for the relationship between the HLA-B*15:02 allele and CBZ-induced TEN/SJS across all populations (71.38; 95% CI = 34.89-146.05).
Conclusions: The present study reveals that CBZ is the leading cause of TEN/SJS in many countries. Screening of HLA-B*15:02 may help patients to prevent the occurrence of CBZ-induced TEN/SJS, especially in populations with a higher (≥5%) risk allele frequency.

Matched MeSH terms: Gene Frequency
DNA polymorphism of D1S80 locus in modern Malay sample population of Sarawak

Hairul Azman Roslan, Nur Hafizah Azizan, Rosmawati Saat

Sains Malaysiana, 2009;38.

The molecular genetic marker, minisatellite locus D1S80 (1p35-p36), is a highly polymorphic variable number of tandem repeats (VNTR). Its polymorphic nature allows for phylogenetic studies, forensic analysis, genetic maps construction and paternity testing to be performed. A study of the hypervariable locus D1S80 was conducted to determine the allele frequency and distribution of this locus in modern Malay in Sarawak population. The polymerase chain reaction technique was employed and results were analysed on polyacrylamide gel. A total of seventy-six DNA samples of unrelated Malay individuals in UNIMAS were collected and examined. The VNTR analysis of the D1S80 locus demonstrated the presence of 17 alleles in the Malay population. Allele with the size of 577 bp (27 repeats) was determined to be the most common in the sample population with the frequency of 0.1641, followed by allele with the size of 561 bp (26 repeats) and 529 bp (24 repeats) whose frequency is 0.1172 and 0.1094, respectively. The smallest allele is allele with the size of 465 bp (20 repeats) whereas the largest is allele with the size of 753 bp (38 repeats). The sample population exhibited 57.8% heterozygosity.

Matched MeSH terms: Gene Frequency
Fulltext Population dataset for 21 simple tandem repeat loci in the Akan population of Ghana

Kofi AE, Hakim HM, Khan HO, Ismail SA, Ghansah A, Haslindawaty ARN, et al.

Data Brief, 2020 Aug;31:105746.
PMID: 32490095 DOI: 10.1016/j.dib.2020.105746

Short tandem repeat (STR) loci are widely used as genetic marker for ancestral and forensic analyses. The latter application includes for paternity testing and DNA profiling of samples collected from scenes of crime and suspects. This survey provides the first dataset for 21 STR loci across the Akan population in Ghana by genotyping of 109 unrelated healthy individuals using Investigator 24plex kit. None of the STR loci screened deviated from Hardy-Weinberg equilibrium after applying Bonferroni correction. Overall, 224 unique alleles were observed with allele frequencies ranging from 0.005 to 0.518. The combined match probability, combined power of exclusion and combined power discrimination were 1 in 4.07 × 10-25, 0.999999999 and 1, respectively. Principal coordinate analysis carried out using 21 STR allele frequency data mapped the Akans with Nigerian subpopulation groups (Hausa, Igbo and Yoruba), but separated from Thais of Thailand, Chechen of Jordan and Tijuana of Mexico.

Matched MeSH terms: Gene Frequency
Population data of six Alu insertions in indigenous groups from Sabah, Malaysia

Kee BP, Chua KH, Lee PC, Lian LH

Ann Hum Biol, 2012 Nov-Dec;39(6):505-10.
PMID: 22989108 DOI: 10.3109/03014460.2012.719548

The present study is the first to report the genetic relatedness of indigenous populations of Sabah, Malaysia, using a set of Indel markers (HS4.32, TPA25, APO, PV92, B65 and HS3.23). The primary aim was to assess the genetic relationships among these populations and with populations from other parts of the world by examining the distribution of these markers.

Matched MeSH terms: Gene Frequency
Distribution of transferrin (Tf) subtypes in several Mongoloid populations of East Asia

Saha N

Ann Hum Biol, 1987 7 1;14(4):349-56.
PMID: 3662433

The distribution of serum transferrin subtypes was determined by PAG electrophoresis and isoelectric focussing in a group of 2288 individuals from 10 Mongoloid populations of East Asia. The sample comprised 857 Chinese from different localities: Singapore (239), Malaysia (228), Taiwan (265), Hong Kong (65), Fouzhou (60); Koreans (332), Filipinos (281), Thais (455), Malays (335) and Indonesians (28). The frequencies of TfC1 varied from 0.73 to 0.79 in the Chinese and from 0.76 to 0.83 in the other Mongoloid populations. TfC3 was observed at a frequency of 0.02 in the Koreans and Chinese from Fouzhou. TfDChi was present in a low frequency (0.01 to 0.03) in all the populations. A low frequency of TfB was also present in all the populations. The phenotypic distribution of transferrin subtypes was at Hardy-Weinberg equilibrium in all the populations.

Matched MeSH terms: Gene Frequency
Association of deleted in liver cancer-1 gene polymorphism with increased risk of chronicity of disease among Malaysian patients with hepatitis B infection

Riazalhosseini B, Mohamed R, Devi Apalasamy Y, Mohamed Z

Pharmacogenet Genomics, 2021 Dec 01;31(9):185-190.
PMID: 34320605 DOI: 10.1097/FPC.0000000000000439

OBJECTIVE: The aim of this study is to examine the association between genetic variations in deleted in liver cancer 1 (DLC1) gene with progression of the hepatitis B virus (HBV) infection.
METHODS: A total of 623 subjects were included in this study, of whom, 423 were chronic hepatitis B (CHB) patients without liver cirrhosis or hepatocellular carcinoma (HCC), 103 CHB with either liver cirrhosis ± HCC and 97 individuals who had resolved HBV. Two single-nucleotide polymorphisms rs3739298 and rs532841 of DLC1 gene were genotyped using the Sequenom MassARRAY platform.
RESULTS: Our results indicated significant differences between the chronic HBV and resolved HBV groups in genotype and allele frequencies of DLC1-rs3739298 [odds ratio (OR) = 2.23; 95% confidence interval (CI): 1.24-3.99; P = 0.007] and (OR = 1.54; 95% CI: 1.07-2.22; P = 0.021), respectively. Moreover, haplotype analysis revealed significant associations between chronicity of HBV with TG and GA haplotypes (P = 0.041 and P = 0.042), respectively.
CONCLUSION: A significant association exists between the rs3739298 variant and susceptibility to CHB infection.

Matched MeSH terms: Gene Frequency
Fulltext Ethnic variation in interleukin-6 -174 (g/c) polymorphism in the malaysian population

Gan GG, Subramaniam R, Lian LH, Nadarajan V

Balkan J Med Genet, 2013 Dec;16(2):53-8.
PMID: 24778564 DOI: 10.2478/bjmg-2013-0032

Interleukin-6 (IL-6) is one of the cytokines that has been well studied and implicated in many diseases including cancers. The frequency of the IL-6 -174 (G/C) polymorphism had been proven to differ in various populations. Malaysia is a country with three major ethnic populations, Malays, Chinese and Indians. In this study, we proposed to determine the G or C allele frequency of the IL-6 -174 polymorphism in these three populations. A total of 348 blood samples were available for analysis. The median age for the subjects was 31 years. There were a total of 245 males and 103 females. A total of 86 Malays (25.0%), 122 Chinese (33.0%) and 140 Indians (40.0%) were genotyped. The result showed a significant difference in the G or C allele frequency of the -174 polymorphism. The total frequencies for the G and C alleles were 91.0 and 9.0%, respectively. In the Malays, the allele frequency of the C allele was 4.0% compared with 19.0% in the Indians. The C allele was not detected in the Chinese population. This finding is the first reported on the Malaysian population and may be important in determining risk of diseases associated with the IL-6 polymorphism in these three populations.

Matched MeSH terms: Gene Frequency
Genetic markers of an aboriginal Taiwanese population

Chen KH, Cann H, Chen TC, Van West B, Cavalli-Sforza L

Am J Phys Anthropol, 1985 Mar;66(3):327-37.
PMID: 3857010

A group of Taiwan aborigines, the Toroko, was typed for 21 classical genetic loci. This is part of an ongoing program aimed at a comprehensive study of Taiwan aborigines. In this first paper a short summary of historical, archeological, and anthropological data in the literature is made, and results of the present survey are compared with older results from other aborigine tribes. An analysis of other neighboring populations from southeast Asia has also been carried out in order to give a preliminary answer to the question of origin of Taiwanese aborigines. Fifteen populations were studied for 13 loci by tree analysis, principal components, and isolation by distance. Tree analysis and principal component analysis gave results in fairly good agreement and indicate three major population clusters: a northeast cluster (Ainu, Korea, Japan, and Ryukyu); a southeast cluster (south China, Thailand, Vietnam, Philippines, Taiwan, and Toroko); and a third cluster including Malaya and Borneo. The positions of Polynesia, Micronesia, and Melanesia are somewhat peripheral. Analysis of the tree shows some potential cases of convergence, perhaps owing to admixture, and of divergence. The analysis of isolation by distance shows that geographic propinquity is a reasonably good predictor of general similarity in this area.

Matched MeSH terms: Gene Frequency
Fulltext The Use of SNPs in Pharmacogenomics Studies

Alwi ZB

Malays J Med Sci, 2005 Jul;12(2):4-12.
PMID: 22605952

Pharmacogenomics is the study of how genetic makeup determines the response to a therapeutic intervention. It has the potential to revolutionize the practice of medicine by individualisation of treatment through the use of novel diagnostic tools. This new science should reduce the trial-and-error approach to the choice of treatment and thereby limit the exposure of patients to drugs that are not effective or are toxic for them. Single Nucleotide Polymorphisms (SNPs) holds the key in defining the risk of an individual's susceptibility to various illnesses and response to drugs. There is an ongoing process of identifying the common, biologically relevant SNPs, in particular those that are associated with the risk of disease. The identification and characterization of large numbers of these SNPs are necessary before we can begin to use them extensively as genetic tools. As SNP allele frequencies vary considerably across human ethnic groups and populations, the SNP consortium has opted to use an ethnically diverse panel to maximize the chances of SNP discovery. Currently most studies are biased deliberately towards coding regions and the data generated from them therefore are unlikely to reflect the overall distribution of SNPs throughout the genome. The SNP consortium protocol was designed to identify SNPs without any bias towards these coding regions. Most pharmacogenomic studies were carried out in heterogeneous clinical trial populations, using case-control or cohort association study designs employing either candidate gene or Linkage disequilibrium (LD) mapping approaches. Concerns about the required patient sample sizes, the extent of LD, the number of SNPs needed in a map, the cost of genotyping SNPs, and the interpretation of results are some of the challenges that surround this field. While LD mapping is appealing in that it is an unbiased approach and allows a comprehensive genome-wide survey, the challenges and limitations are significant. An alternative such as the candidate gene approach does offer several advantages over LD mapping. Ultimately, as all human genes are discovered, the need for random SNP markers diminishes and gene-based SNP approaches will predominate. The challenges will then be to demonstrate convincing links between genetic variation and drug responses and to translate that information into useful pharmacogenomic tests.

Matched MeSH terms: Gene Frequency
Fulltext Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population

Tee SF, Chow TJ, Tang PY, Loh HC

Genet. Mol. Res., 2010;9(3):1274-8.
PMID: 20623453 DOI: 10.4238/vol9-3gmr789

The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.

Matched MeSH terms: Gene Frequency/genetics
Glyoxalase I Ala111Glu gene polymorphism: No association with breast cancer risk but correlated with absence of progesterone receptor

Naidu R, Har YC, Taib NA

Pathol. Int., 2010 Sep;60(9):614-20.
PMID: 20712647 DOI: 10.1111/j.1440-1827.2010.02568.x

The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer.

Study site: Universiti Malaya Medical Centre (UMMC)

Matched MeSH terms: Gene Frequency/genetics
Contribution of GABRG2 Polymorphisms to Risk of Epilepsy and Febrile Seizure: a Multicenter Cohort Study and Meta-analysis

Haerian BS, Baum L, Kwan P, Cherny SS, Shin JG, Kim SE, et al.

Mol Neurobiol, 2016 10;53(8):5457-67.
PMID: 26452361 DOI: 10.1007/s12035-015-9457-y

Gamma-aminobutyric acid receptor (GABA-A) is the most common receptor of fast synaptic inhibition in the human brain. Gamma protein encoded by the GABRG2 gene is one of the subunits of the GABA-A receptor, which plays an essential role in the function of this receptor. Several studies have identified various febrile seizure (FS) and epilepsy risk variants of GABRG2 gene in different populations, but some others did not support these results. The aim of this case-control study is to investigate whether GABRG2 polymorphisms contribute to susceptibility for FS and epilepsy in pooled data of three cohorts, from Malaysia (composed of Malay, Chinese, and Indian), Hong Kong, and Korea. Furthermore, the pooled dataset of these cohorts with previous reports were meta-analyzed for determining the risk effect size of the rs211037 polymorphism on FS and symptomatic epilepsy (SE). The rs211037, rs210987, rs440218, rs2422106, rs211014, and rs401750 polymorphisms were genotyped in the 6442 subjects (1729 epilepsy and 4713 controls). Results of the case-control study showed associations between rs211037 and the risk of SE in the pooled data from all cohorts (T vs. C, p = 3 × 10(-5), and TT vs. CC, p = 2 × 10(-5)) and the risk of partial seizure in the combined data of Malaysia and Hong Kong (both T vs. C and TT vs. CC, p = 2 × 10(-6)). The rs211037-rs210987 and rs2422106-rs211014-rs401750 haplotypes were also associated with susceptibility to SE in Chinese. Meta-analysis of all Asians identified association between rs211037 and FS and SE (T vs. C, p = 4 × 10(-4), and p = 4 × 10(-3), respectively). In conclusion, rs211037 alone may be a risk factor for FS, partial seizure, and SE, and in linkage disequilibrium with rs210987 can contribute to FS and SE in Asians, particularly in Chinese.

Matched MeSH terms: Gene Frequency/genetics
CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study

Tan YH, Sidik SM, Syed Husain SN, Lye MS, Chong PP

Asian Pac J Cancer Prev, 2016;17(1):57-64.
PMID: 26838255

BACKGROUND: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism.
MATERIALS AND METHODS: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR.
RESULTS: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia.
CONCLUSIONS: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.

Matched MeSH terms: Gene Frequency/genetics
Fulltext Association between PDCD1 gene polymorphisms and risk of systemic lupus erythematosus in three main ethnic groups of the Malaysian population

Chua KH, Lian LH, Sim XJ, Cheah TE, Lau TP

Int J Mol Sci, 2015;16(5):9794-803.
PMID: 25938972 DOI: 10.3390/ijms16059794

The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants.

Matched MeSH terms: Gene Frequency/genetics
Variation of the platelet glycoprotein IIIa PI(A1/A2) allele frequencies in the three ethnic groups of Singapore

Lim J, Lal S, Ng KC, Ng KS, Saha N, Heng CK

Int J Cardiol, 2003 Aug;90(2-3):269-73.
PMID: 12957761

BACKGROUND: Polymorphisms of the glycoprotein IIIa receptor have been shown to be associated with differences in platelet aggregability. The PI(A2) variant of the polymorphism has been reported to be an inherited risk factor for acute coronary events. Although the allele frequency of this polymorphism is well documented in Caucasian populations, studies involving Asian Indians, Malays and Chinese are lacking. We studied 706 random male individuals to determine the genotypic distribution of this polymorphism in Singapore.
METHODS: Male subjects included in this study were drawn from those undergoing routine annual medical examinations offered by their employers. Venous blood was obtained from these patients after an overnight fast and from which genomic DNA was extracted. Genotyping was carried out by polymerase chain reaction (PCR) followed by digestion with restriction enzyme NciI. Personal and family medical history of the subjects were also taken.
RESULTS: The genotype distribution of the individuals studied was in accordance to a population at Hardy Weinberg equilibrium. The frequency of the PI(A2) allele was 0.1, 0.01 and 0.01 in the Indians, Malays and Chinese, respectively. The differences in frequencies of the PI(A2) variant are significant among different ethnic groups (P<0.001 for Indians vs. Chinese and Indians vs. Malays).
CONCLUSIONS: We observed a significantly higher frequency of the PI(A2) allele among Indians relative to the Chinese and Malays in Singapore. The effect of this genotype may partially explain the higher rate of ischaemic heart disease seen among Indians compared to the Chinese and Malay ethnic groups.

Matched MeSH terms: Gene Frequency*
Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects

Gan SH, Ismail R, Wan Adnan WA, Wan Z

J Pharm Biomed Anal, 2002 Sep 05;30(2):189-195.
PMID: 12191703

The aim of the present study is to investigate the influence of the CYP2D6*10 allele on the disposition of tramadol hydrochloride in Malaysian subjects. A single dose of 100 mg tramadol was given intravenously to 30 healthy orthopaedic patients undergoing various elective surgeries. After having obtained written informed consents, patients were genotyped for CYP2D6*10: the most common CYP2D6 allele among Asians by means of allele-specific polymerase chain reaction. The presence of other mutations (CYP2D6*1, *3, *4, *5, *9 and *17) was also investigated. Tramadol was extracted from 1 ml serum with an n-hexane: ethylacetate combination (4:1) after alkalinisation with ammonia (pH 10.6). Serum concentrations were measured by means of high-performance liquid chromatography. The pharmacokinetics of tramadol was studied during the 24 h after the dose. As among other Asians, the allele frequency for CYP2D6*10 among Malaysians was high (0.43). Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test). When patients were screened for the presence of other alleles, the pharmacokinetic parameter values were better explained. CYP2D6 activity may play a main role in determining tramadol pharmacokinetics. The CYP2D6*10 allele particularly was associated with higher serum levels of tramadol compared with the CYP2D6*1 allele. However, genotyping for CYP2D6*10 alone is not sufficient to explain tramadol disposition.

Matched MeSH terms: Gene Frequency/genetics
Comparison of the complete nucleotide sequences of echovirus 7 strain UMMC and the prototype (Wallace) strain demonstrates significant genetic drift over time

Chua BH, McMinn PC, Lam SK, Chua KB

J Gen Virol, 2001 Nov;82(Pt 11):2629-39.
PMID: 11602774

The complete nucleotide sequences are reported of two strains of echovirus 7, the prototype Wallace strain (Eo7-Wallace) and a recent Malaysian strain isolated from the cerebrospinal fluid of a child with fatal encephalomyelitis (Eo7-UMMC strain). The molecular findings corroborate the serological placement of the UMMC strain as echovirus 7. Both Eo7-Wallace and Eo7-UMMC belong to the species human enterovirus B and are most closely related to echovirus 11. Eo7-UMMC has undergone significant genetic drift from the prototype strain in the 47 years that separate the isolation of the two viruses. Phylogenetic analysis revealed that Eo7-UMMC did not arise from recombination with another enterovirus serotype. The molecular basis for the severely neurovirulent phenotype of Eo7-UMMC remains unknown. However, it is shown that mutations in the nucleotide sequence of the 5' untranslated region (UTR) of Eo7-UMMC result in changes to the putative structure of the 5' UTR. It is possible that these changes contribute to the neurovirulence of Eo7-UMMC.

Matched MeSH terms: Gene Frequency*
Genetic factors and malaria in the Temuan

Baer A, Lie-Injo LE, Welch QB, Lewis AN

Am J Hum Genet, 1976 Mar;28(2):179-88.
PMID: 817597

The jungle habitat of the Temuan aborigines harbors a variety of infectious diseases, the most notable being malaria. Our study of 15 genetic systems in the Temuan revealed substantial polymorphism and within-population genetic diversity. The polymorphisms for Hb beta, G6PD, and El are of interest in regard to genetic adaptation to malaria. Among the polymorphisms investigated we conclude that G6PD deficiency and elliptocytosis are likely to have malaria-resistant effects as evidenced by their low association with malarial parasitemia or their higher frequency in adults than in children. These findings suggest that the malarial habitat of the Temuans is livable in the long range sense for them because of the cluster of malaria-resistant alleles in their gene pool (G6PD)-, El, and possibly, but not tested here because of its low frequency, Hb beta E). The same condition probably holds for the Semai, the nearest aborigine neighbors of the Temuan (although the Semai have not been tested for malarial parasitemia and for these polymorphisms simultaneously), since the Semai have substantial Hb betaE, G6PD-, and El. The Temuan have a cultural identity system of rituals, beliefs, and certain aspects of language which effectively isolates them genetically from Malays and other nonaborigines. This system hinders the dilution of the malaria-resistant alleles of the Temuan gene pool with the malaria-susceptible alleles of the nonaborigine gene pools.

Matched MeSH terms: Gene Frequency*
Variation of several erythrocyte enzymes in the Dayaks of Sarawak

Ganesan J, Lie-Injo LE, Ong Beng P

Hum. Hered., 1976;26(2):124-7.
PMID: 181317

The Land and Sea Dayaks of Sarawak were surveyed for several erythrocyte enzymes. The gene frequency of 6PGDC in 132 Land Dayaks and 127 Sea Dayaks were 0.045 and 0.047, respectively. The gene frequency of PGM1-1 IN 285 Land Dayks and 240 Sea Dayaks were 0.716 and 0.779, respectively. The ADA2 gene frequency in 283 Land Dayaks and 188 Sea Dayaks were 0.154 and 0.090. ADA 5-1 was found once in the Land Dayaks and once in the Sea Dayaks. AK 2-1 was found once in 221 Sea Dayaks but not in any of 270 Land Dayaks. No PHI, LDH or CA variants were found among the Land or Sea Dayaks.

Matched MeSH terms: Gene Frequency*

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