Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM), as well as in cardiovascular diseases (CVD). The Leptin Receptor (LEPR) gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF) criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR) method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05).
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
Chronic kidney disease (CKD) is an emerging public health problem worldwide. Previous studies have shown an association between blood pressure (BP) and CKD. However, it is not clear if there are ethnic differences in this association. We examined the association between BP and CKD in a multi-ethnic Asian population in Singapore.
Matched MeSH terms: Asian Continental Ancestry Group/ethnology*
Diabetic retinopathy is the most common diabetic eye disease, occurring in about 60% of type 2 diabetic patients. Other than known clinical risk factors, the influence of genes has been suggested as part of the development of diabetic retinopathy. We investigated the association of Gly82Ser, 1704G/T and 2184A/G polymorphisms in the RAGE gene with retinopathy in type 2 diabetic patients in Malaysia. Ninety-eight unrelated retinopathy patients and 185 unrelated healthy controls from all over Malaysia were recruited in this study. The allele and genotype frequencies of the three gene polymorphisms were investigated using PCR-RFLP. The allele frequency of the three polymorphisms did not differ significantly between the control and the retinopathy group (P > 0.05). Analysis of the frequency of GA+AA, GT+TT and AG+GG in the retinopathy group did not reveal significant differences (P > 0.05) compared to the control group. We conclude that RAGE gene Gly82Ser, 1704G/T and 2184A/G polymorphisms are not associated with retinopathy development in the Malaysian population.
Matched MeSH terms: Asian Continental Ancestry Group/genetics
To evaluate corneal thickness and volume in subclinical and clinical keratoconus in Asian population with the aim of discriminating between normal and ectatic cornea. Eyes were placed into one of the following three groups: normal, subclinical, and mild-moderate keratoconus. Pentacam Scheimpflug imaging (Oculus Inc., Wetzlar, Germany) was performed for each participant to record thinnest corneal thickness, central corneal thickness, corneal volume (CV), peripheral corneal thickness (PCT) and percentage thickness increase (PTI) at 2, 4, 6, and 8 mm. The data were exported to SPSS for statistical analysis. Subjects comprised 52 normal, 15 subclinical keratoconus, and 32 mild-moderate clinical keratoconus eyes. Our results indicated that corneal thickness (CT) distribution, PTI, and CV in normal eyes were significantly different compared with subclinical and clinical keratoconus (P < .05). Overall, subclinical group exhibited lower CT distribution and volume, and higher PTI in comparison with normal eyes. However, they showed higher CT distribution and volume, and lower PTI compared with keratoconus group. In addition, there was a smaller change in PCT and PTI from the thinnest point of the cornea to the periphery. The results of the present study indicate that CT parameters and CV were significantly different in normal versus subclinical group and in normal versus keratoconus group. These findings could help clinicians to better discriminate between normal and ectatic cornea.
Matched MeSH terms: Asian Continental Ancestry Group/statistics & numerical data*
Ischemic heart disease and stroke are the two leading causes of death worldwide. Antiplatelet therapy plays the most significant role in the management of these cardiovascular and cerebrovascular occlusive events to prevent recurrent ischemic attack. Clopidogrel, an antiplatelet drug, is widely prescribed either alone or in combination with aspirin as dual antiplatelet therapy for the prevention of vascular occlusive events. The antiplatelet response to clopidogrel varies widely. Hyporesponders and nonresponders are likely to have adverse cardiovascular events during follow-up. Some drugs, such as proton pump inhibitors (omeprazole), calcium channel blockers, selective serotonin reuptake inhibitors (nefazadone), coumarin derivatives (phenprocoumon), benzodiazepines, sulfonylurea, erythromycin, and itraconazole, decrease the antiplatelet effect of clopidogrel when administered concomitantly. Decreased response to clopidogrel is common among Asians due to genetic polymorphisms associated with clopidogrel resistance, and it is nearly 70% in some of the Asian communities. It is necessary to study Asian populations, because there are a large number of Asians throughout the world due to increased migration. Current guidelines do not make genetic testing or platelet response testing mandatory prior to clopidogrel prescription. Therefore, it is important for clinicians treating Asian patients to keep in mind the interindividual variability in response to clopidogrel when prescribing the drug.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.
Matched MeSH terms: Asian Continental Ancestry Group/genetics
Familial hypercholesterolemia (FH) is a disease implicated with defects in either, Low density lipoprotein receptor gene (LDLR), Apolipoprotein B-100 gene (APOB), the Proprotein convertase subtilisin/kexin type 9 gene (PCSK9) or other related genes of the lipid metabolism pathway. The general characterization of heterozygous FH is by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular diseases, while the more severe type, the homozygous FH results in extreme elevated levels of LDL cholesterol and usually death of an affected individual by early twenties. We present here a novel non-synonymous, missense mutation in exon 14 of the LDLR gene in two siblings of the Malay ethnicity discovered during an in-house genetic test. We postulate that their elevated cholesterol is due to this novel mutation and they are positive for homozygous FH. This is the first report of a C711Y mutation in patients with elevated cholesterol in Asia.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10(-5); OR = 1.9, P = 5.2 × 10(-5); OR = 1.9, P = 7.8 × 10(-5), respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D.
Matched MeSH terms: Asian Continental Ancestry Group/genetics
Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P=0.001, odds ratio=2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition.
Matched MeSH terms: Asian Continental Ancestry Group/genetics
Recent studies associated the HLA-B 1502 allele with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients from China, Thailand and Malaysia. No association has been found in patients from Europe or Japan. Linkage summary reports from East and South-east Asia predict a highly significant odds ratio (OR) of 84.75 (95% confidence interval [CI]=42.53-168.91; p=8.96×10[-15]) with sensitivity and negative predictive values of 92% and 98%, respectively. The higher prevalence of HLA-B 1502 allele among certain Asian populations (10-15%) compared to Caucasians (1-2%) may explain a 10-fold to 25-fold higher incidence of CBZ-SJS/TEN in patients from Asia. Screening for HLA-B 1502 before using CBZ can prevent SJS/TEN in certain populations, but screening may be less beneficial in populations with low HLA-B 1502 allele frequency and in patients exposed to CBZ for more than 2 months. A retrospective study demonstrated that the costs of HLA-B 1502 screening were less than those of SJS treatment. This article reviews possible benefits and concerns of HLA-B 1502 screening in clinical practice.
Matched MeSH terms: Asian Continental Ancestry Group/genetics
The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS, gene symbol: PTS) is involved in the second step of the de novo biosynthesis of tetrahydrobiopterin (BH4), which is a vital cofactor of nitric oxide synthases and three types of aromatic amino acid hydroxylases; the latter are important enzymes in the production of neurotransmitters. We conducted a study of PTS mutations in East Asia, including Taiwan, Mainland China, Japan, South Korea, the Philippines, Thailand and Malaysia. A total of 43 mutations were identified, comprising 22 previously reported mutations and 21 new discovered mutations. Among these, the c.155A>G, c.259C>T, c. 272A>G, c.286G>A and c.84-291A>G mutations were the most common PTS mutations in East Asia, while the c.58T>C and c.243G>A mutations were, respectively, specific to Filipinos and Japanese originating from Okinawa. Further studies demonstrated that each of the mutations listed above was in linkage disequilibrium to a specific allele of polymorphic microsatellite marker, D11S1347. These results suggest the presence of founder effects that have affected these frequent mutations in East Asia populations. In this context, D11S1347 should become one of the most reliable polymorphic markers for use in prenatal diagnosis among PTPS deficient families, especially where mutations are yet to be identified.
Matched MeSH terms: Asian Continental Ancestry Group*
Hereditary pancreatitis (HP) is a very rare form of early-onset chronic pancreatitis, which usually begins in childhood with a variable spectrum of severity of disease. HP is commonly caused by variants/mutations in the PRSS1 gene as reported in many studies. Therefore, in this study, we aimed to investigate the possible association of PRSS1 gene variants/mutations in a Malaysian Chinese family with HP.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
To develop and cross-validate bioelectrical impedance analysis (BIA) prediction equations of total body water (TBW) and fat-free mass (FFM) for Asian pre-pubertal children from China, Lebanon, Malaysia, Philippines and Thailand.
Matched MeSH terms: Asian Continental Ancestry Group*
BACKGROUND AND AIM:
Outcome measures for clinical trials in dyspepsia require an assessment of symptom response. There is a lack of validated instruments assessing dyspepsia symptoms in the Asian region. We aimed to translate and validate the Leeds Dyspepsia Questionnaire (LDQ) in a multi-ethnic Asian population.
METHODS:
A Malay and culturally adapted English version of the LDQ were developed according to established protocols. Psychometric evaluation was performed by assessing the validity, internal consistency, test-retest reliability and responsiveness of the instruments in both primary and secondary care patients.
RESULTS:
Between April and September 2010, both Malay (n=166) and Malaysian English (n=154) versions were assessed in primary and secondary care patients. Both language versions were found to be reliable (internal consistency was 0.80 and 0.74 (Cronbach's α) for Malay and English, respectively; spearman's correlation coefficient for test-retest reliability was 0.98 for both versions), valid (area under receiver operating curve for accuracy of diagnosing dyspepsia was 0.71 and 0.77 for Malay and English versions, respectively), discriminative (median LDQ score discriminated between primary and secondary care patients in Malay (11.0 vs 20.0, P<0.0001) and English (10.0 vs 14.0, P=0.001), and responsive (median LDQ score reduced after treatment in Malay (17.0 to 14.0, P=0.08) and English (18.0 to 11.0, P=0.008) to dyspepsia.
CONCLUSIONS:
The Malaysian versions of the LDQ are valid, reliable and responsive instruments for assessing symptoms in a multi-ethnic Asian population with dyspepsia.
Matched MeSH terms: Asian Continental Ancestry Group/statistics & numerical data*
Appropriate screening for irregular red-cell antibodies is essential for ensuring transfusion compatibility and for antenatal management of mothers at risk of haemolytic disease of the foetus and newborn. Screening for all relevant antibodies is, however, limited by screening cells that do not express antigens present in the patient and donor population. Technology to artificially incorporate antigens into red cells is currently available and may be an option for customizing screening cells.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
BACKGROUND: Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population.
OBJECTIVES: This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population.
METHODS: A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared.
RESULTS: HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries.
CONCLUSIONS: HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.
Matched MeSH terms: Asian Continental Ancestry Group/genetics
Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻⁹). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹⁶) and rs12447690 (p(meta) = 1.92 × 10⁻¹⁴)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻⁹). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*
CYP1A2 play an important role in the metabolism of many carcinogens and clinically important drugs. CYP1A2 activity has been found to be influenced by the presence of polymorphic variants which were reported to display wide interethnic variation. This study investigates the frequency distribution and linkage disequilibrium patterns of CYP1A2 genetic polymorphisms, and characterize their haplotype structures in three healthy Asian populations in Singapore (Chinese, Malay, and Indian). The entire CYP1A2 gene was screened in 126 healthy subjects from all three ethnic groups (N=42 each). A total of 25 polymorphisms was identified, of which nine were novel. The polymorphisms, -2467delT and -163C>A were detected at high frequencies in all Asian ethnic groups. Significant interethnic differences were observed in the genotypic frequency distribution of IVS2-99G>A (P<0.01) and 1548C>T (P=0.05) across the three ethnic groups while -163C>A (P=0.02) was found to differ between Chinese and Malays. Haplotype analyses revealed four to six major haplotypes in each ethnic population which accounted for more than 60% of the cumulative haplotype frequencies. Future studies should be done to investigate the functional roles of these haplotypes.
Matched MeSH terms: Asian Continental Ancestry Group/genetics*