Mitochondrial malic enzyme polymorphism among different ethnic groups in Singapore

Mitochondrial malic enzyme (EC 1.1.1.40; MEM) was examined by starch-gel electrophoresis on post-mortem brain samples from 453 unrelated subjects of either sex comprising 161 Chinese, 150 Indians and 113 Malays and 29 from other racial groups. The estimated gene frequencies of MEM1 were found to be 0.7111, 0.6100 and 0.6769 in Chinese, Indians and Malays, respectively. No significant deviation from the Hardy-Weinberg equilibrium was observed in Chinese and Malays. However, there was a significant deviation with a deficiency of heterozygotes among Indians. MES did not show any polymorphism.     

Salivary proline-rich protein polymorphisms in Chinese, Malays and Indians in Singapore

Salivary proline-rich protein (PRP) polymorphism, PRH1, PRH2, Ps, Pm (PmF), PmS and Gl, were investigated in three ethnic groups in Singapore: Chinese, Malays and Indians. The phenotype and gene frequencies were presented and comparison with other ethnic groups was made. The As protein, which was recently found in Japanese but not in Caucasians as a new allelic product of the PRH1 locus, was also observed in Chinese and Malays but not in Indians. Another allelic product (Ps4) of Ps protein polymorphism was found in Malays but not in Chinese and Indians. The results indicate the usefulness of salivary PRP polymorphism as markers in population genetic studies.     

alpha1-Antitrypsin variants in different racial groups in Malaysia.

In a study of Malaysians of different racial groups, 1,510 sera (908 from Malays, 371 from Chinese and 231 from Indians) were identified for their protease inhibitor (Pi) types. The gene frequencies for the alleles PiM, PiS and PiX in Malays were, respectively, 0.979, 0.015, and 0.007. In Chinese, the frequencies were 0.981, 0.019 and 0.000, and in Indians they were 0.976, 0.24, and 0.000. It is interesting that the usually rare PiX type is found in appreciable frequency in the Malays. Two different types with unusual behavior and obscure origin were also found.     

gamma-Aminobutyric acid transaminase (GABAT) polymorphism among ethnic groups in Singapore--with report of a new allele.

gamma-Aminobutyric acid transaminase (GABAT, E.C.2.6.I.19) was phenotyped by starch-gel electrophoresis in post-mortem liver samples from 650 unrelated subjects of either sex, comprising 289 Chinese, 177 Indians, 140 Malays, and 44 from other racial groups from Southeast Asia. The estimated gene frequencies of GABAT1 and GABAT2 were found to be .5779 and .3806 in Chinese, .5678 and .3955 in Indians, and .6214 and .3250 in Malays. The frequency of GABAT1 was .5909 in the mixed group of other races. There was no significant difference in the phenotypic distribution between sexes. A new slow (less anodal) variant (GABAT3) has been observed in low frequency in all the groups (.0415, .0367, 0536, and 0536, and .0568 in Chinese, Indians, Malays, and the mixed-group, respectively). The distribution of GABAT phenotypes was at Hardy-Weinberg equilibrium in all the ethnic groups studied.     

The 27-bp VNTR Polymorphism in Intron 4 of the Human eNOS Gene in Healthy Singaporean Chinese, Indians, and Malays

Human endothelial nitric oxide synthase (eNOS) is one isoform of the nitric oxide synthases that are responsible for nitric oxide synthesis from L-arginine. The gene encoding eNOS contains a 27-bp VNTR polymorphism in intron 4. We report here for the first time the presence of a novel allele 3, which was absent in all other populations studied to date, in 1.7% each of Singaporean Indians and Malays. We also detected the presence of a novel genotype 3/5 in 3.4% each of Singaporean Indians and Malays. Allele 6, which was absent in Han Chinese from northern China and Taiwan and was also absent in Indians from the Indian subcontinent, was found in 2.1% of Singaporean Chinese and in 0.3% of Singaporean Indians.     

Salivary peroxidase,Pm, and Ph protein polymorphisms in Malaysians

Summary Three human saliva genetic markers, namely, salivary peroxidase (SAPX), Pm, and Ph proteins, were investigated in the three major ethnic groups of Malaysia: Malays, Chinese, and Indians.For Pm, the allelic frequencies of Pm ⁺ for Malays, Chinese, and Indians are 0.385±0.030, 0.282±0.026, and 0.289±0.026 respectively. For Ph, the allelic frequencies of Ph ⁺ are 0.082±0.016 for Malays, 0.109±0.017 for Chinese, and 0.062±0.013 for Indians. For SAPX, the allelic frequencies of SAPX ¹ in Malays, Chinese, and Indians are 0.762±0.027, 0.755±0.027, and 0.723±0.026 respectively.     

Apolipoprotein A-IV polymorphism in Singapore ethnic groups

A total of 627 subjects comprising 455 Chinese, 127 Dravidian Indians and 45 Malays were investigated for serum Apo A-IV polymorphism. The frequency of Apo A-IV*2 was found to be significantly higher (p less than 0.001) in Indians (0.043) compared to that in the Chinese (0.010) and Malays (0.011). The frequency of A-IV*3 was found to be around 0.02 in all the ethnic groups. A low frequency of A-IV*4 (less than 0.01) was observed in the Chinese and Indians. The phenotypic distribution of Apo A-IV was at Hardy-Weinberg equilibrium in the three ethnic groups.     

<Emphasis Type="Italic">ABCA1</Emphasis> gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore

Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.     

Erythrocyte adenosine deaminase in Malaysians.

944 adenosine deaminase phenotypings of Malay, Chinese, and Indian blood donors and newborns at Kuala Lumpur, Malaysia, yielded ADA1 gene frequency estimates of 0.885 for the Malays, 0.939 for the Chinese, and 0.853 for the Indians.     

cagA gene variants in Malaysian Helicobacter pylori strains isolated from patients of different ethnic groups

Helicobacter pylori infection of a distinct subtype of cagA may lead to different pathological manifestation. The aim of this study is to determine the presence of cagA gene and its variants in H. pylori infection among different ethnic groups and its effect on gastroduodenal diseases. Overall detection of cagA among the 205 clinical isolates of H. pylori was 94%. Variations in size of the 3' region of cagA gene were examined among 192 Malaysian H. pylori cagA-positive strains. Results showed that three cagA variants differing in fragment length of PCR products were detected and designated as type A (621-651bp), type B (732-735bp) and type C (525 bp). Although there was no association between any of the cagA subtypes with peptic ulcer disease (p>0.05), an association between cagA subtypes with a specific ethnic group was observed. Specific-cagA subtype A strains were predominantly isolated from Chinese compared to Malays and Indians (p<0.0005), and cagA subtype B strains were predominantly isolated from Malays and Indians compared to Chinese (p<0.05). The cagA type A strains of H. pylori is commonly found in the Chinese patients who have a higher risk of peptic ulcer disease, thus indicating that it could be used as an important clinical biomarker for a more severe infection.     

New AccI polymorphism in the follicle-stimulating hormone beta-subunit gene and its prevalence in three Southeast Asian populations.

A thymine-cytosine substitution was identified in exon 3 (codon 76, TAT to TAC) of the human follicle-stimulating hormone (FSH) beta-subunit gene. The nucleotide change led to creation of an AccI digestion site. The frequencies of the A allele (with AccI site) in Chinese (n = 201), Malays (n = 168) and Indians (n = 132) were 0.358, 0.333 and 0.402, respectively. The new FSH beta-subunit marker may be useful in gene tracking and association studies.     

Apolipoprotein H (beta-2-glycoprotein I) polymorphism in Asians.

Apolipoprotein H (APOH) (beta-2-glycoprotein I) polymorphism has been studied in 1159 Asians. The sample included 872 Chinese, 179 Asiatic Indians (Dravidian), 91 Filipinos, and 17 Malays. APOH polymorphism was determined by isoelectric focusing of sera in thin-layer polyacrylamide gels containing 3 M urea followed by immunoblotting. The frequencies of the three alleles--APOH*1, APOH*2, and APOH*3--were found to be 0.031, 0.900, and 0.069 in the Chinese; 0.061, 0.866, and 0.073 in the Dravidian Indians; 0.055, 0.923, and 0.022 in the Filipinos; and 0.088, 0.882, and 0.029 in the Malays. The phenotypic distribution was at Hardy-Weinberg equilibrium in all the populations.     

Population genetics of coagulant factor IX: frequencies of two DNA polymorphisms in five ethnic groups.

Two frequently used restriction-enzyme polymorphisms (RFLPs) of coagulant F.IX, TaqI and XmnI, have been examined in five ethnic groups: white Americans, black Americans, East Indians, Chinese, and Malays. There is a distinct "cline" in the frequencies of both polymorphisms, from white Americans to Malays. The rarer type 2 alleles of both polymorphisms, in which middle recognition sites are present--and which in our sample reach their highest frequencies in white Americans--are marginally higher in four groups of Europeans previously reported by others. The frequencies of the rarer alleles are significantly higher in Europeans than in black Americans and East Indians, and these alleles are essentially absent in Chinese and Malays. The frequency of heterozygosity diminishes in the same order, being zero in Malays for both polymorphisms. The polymorphisms are in strong linkage disequilibrium, and in all groups the type 1 allele for TaqI is disproportionately accompanied by the type 1 allele for XmnI. The paucity of type 2 alleles and the low rate of heterozygosity in four non-European groups suggest that the polymorphisms will be of little diagnostic value south of Gibraltar and east of Suez. This prediction is confirmed by the observed haplotype frequencies in the black American and the Oriental groups.     

Acid alpha-glucosidase in Malaysians. Population studies and the occurrence of a new variant.

Acid alpha-glucosidase from the placenta was electrophoretically surveyed in a total of 633 Malaysians, 236 of Malay, 261 of Chinese and 136 of Indian ancestries. A new variant, alpha-glucosidase 3-1 was observed in 1 Malay and 3 Indians. A polymorphism for this enzyme was observed among Indians, but in Chinese and Malays variants are rare. Phenotype 2-1 was observed once in a Chinese and once in a Malay.     

Daten zur Populationsgenetik der 6-Phosphogluconat-Dehydrogenase

Summary Four Malaysian racial groups were typed for red cell adenylate kinase: 324 Malays, 300 Chinese, 256 Indians, and 483 West Malaysian Aborigines. The AK² gene frequencies found were 0.015, 0.0, 0.086, and 0.013, respectively. All 244 Malays, 170 Chinese, 153 Indians, and 132 West Malaysian Aborigines examined had the common cytoplasmic malate dehydrogenase phenotype.

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Zusammenfassung Vier Rassengruppen aus Malaysia wurden auf Adenylatkinase-Varianten hin untersucht: 324 Malayen, 300 Chinesen, 256 Inder und 483 Eingeborene von West-Malaysia. Die Genhäufigkeiten des Allels AK² waren: 0,015, 0,0, 0,086 und 0,013. Alle 244 Malayen, 170 Chinesen, 153 Inder und 132 west-malaysischen Eingeborenen, die daraufhin untersucht werden konnten, hatten den häufigen Phänotyp der cytoplasmatischen Malat-Dehydrogenase.

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This work was supported by the University of Maryland and University of California International Centers for Medical Research and Training with research grants AI-10049-12, AI-10051, and HE 10486, all from the National Institutes of Health, U.S. Public Health Service.     

Hardy–Weinberg Disequilibrium of the IL-18 C?607A SNP Suggesting Selective Advantage of Heterozygotes

Interleukin-18 (IL-18) plays a key role in autoimmune, inflammatory, and infectious diseases. The IL-18 gene contains a C to A single nucleotide polymorphism (SNP) at position -607 (C-607A) within the promoter region, which was found to affect the promoter activity and subsequently the protein level of IL-18. We investigated this SNP in a group of healthy Singaporeans and found that CA was the most common genotype and the C allele was more prevalent than the A allele, which was not always the case in other ethnic groups. In addition, Singaporean Chinese were significantly different from Singaporean Indians in both allelic and genotypic distributions. Furthermore, significant deviations from Hardy-Weinberg equilibrium of this SNP were found in all three ethnic groups studied (Chinese, Indians, and Malays) and also in other published literature, suggesting that heterozygotes of this IL-18 C-607A SNP may have certain selective advantages.     

Ethnic fertility differentials in Peninsular Malaysia and Singapore

Differences in fertility between the three major ethnic groups (Malays, Chinese and Indians) in Peninsular Malaysia and Singapore have existed since before the onset of fertility decline in the late 1950s and remain today, although the relative positions and the actual differences have changed due to the varying rates of decline. By 1987, the Malays experienced the highest fertility and the Chinese the lowest in both countries but in Singapore the Malay fertility was lower than the Chinese fertility in Peninsular Malaysia. The fertility differentials will lead to changes in the ethnic composition in both countries but more so in Peninsular Malaysia.     

Acyl-CoA: cholesterol acyltransferase-2 gene polymorphisms and their association with plasma lipids and coronary artery disease risks

Acyl-CoA: cholesterol acyltransferase-2 (ACAT2), an intracellular cholesterol esterification enzyme found only in the intestine and liver, has been demonstrated to be associated with hypercholesterolemia and atherosclerosis in mice. To explore the possible impact of ACAT2 gene variants on CAD susceptibility and plasma lipid levels, three polymorphisms, 41A>G (Glu>Gly), 734C>T (Thr>Ile), and IVS4-57_58 ins48 bp (D/I), were genotyped in 809 CAD patients (CAD+) and 1,304 controls (CAD−) from three distinct Singaporean ethnic groups (1,228 Chinese, 367 Malays and 518 Indians). The 734T allele frequency was significantly lower in CAD+ (0.20) than CAD− (0.26) in Chinese (P=0.003) and I allele of D/I was significantly higher in CAD+ (0.17) than CAD− (0.10) in Indians (P=0.011). The 41G allele was significantly more frequent among normolipidemic (0.19) than dyslipidemic (0.13) individuals in Chinese (P=0.008). In normolipidemic females, 734C>T was associated with apoA1, apoB and lipoprotein (a) in Indians, and with apoA1 in Malays, whereas 41A>G is associated with total cholesterol in Indians. The 734C>T polymorphism was in almost complete linkage disequilibrium (LD) with the IVS4-57_58 ins48 bp and in very strong LD with 41A>G in all the three ethnic groups. In the normolipidemic females, the AG/CT had much higher apoB than AA/CC in Indians. We found that the three ACAT2 polymorphisms studied are associated with CAD risk and plasma lipid levels but their effects are not consistent across genders and ethnic groups.     

Glucose dehydrogenase polymorphism among ethnic groups of Singapore--with report of two additional alleles (GDH4 and GDH5).

Placental glucose dehydrogenase (GDH; E.C.1.1.1.47) polymorphism was studied in 254 Chinese, 104 Malays, and 47 Indians from Singapore using isoelectric focusing. There is suggestive evidence of two additional anodal alleles (GDH4 and GDH5) in addition to the three alleles described in earlier studies. Altogether, 14 phenotypes have been observed in the present investigation, compared with six phenotypes described in earlier studies. It appears that placental GDH is controlled by five codominant autosomal alleles producing 15 possible phenotypes. The gene frequencies of GDH1, GDH2, and GDH3 in these ethnic groups are significantly different from those reported in Caucasians. There were slight differences in the gene frequencies between the three ethnic groups, with those of Indians being nearer to the frequency in Caucasians. In general, the distribution of GDH phenotypes was at Hardy-Weinberg equilibrium in all three ethnic groups studied.     

Ethnic Variation in the Correlation Between Fasting Glucose Concentration and Glycated Hemoglobin (HbA1C)

ObjectiveWe aimed to determine the relationship between fasting serum glucose (FSG) concentration and glycated hemoglobin-Alc (HbAlc) in the 3 ethnicities in Singapore after adjustment for demographic and therapeutic variables.MethodsFasting serum glucose (FSG), HbAlc, and serum creatinine levels were simultaneously sampled from 575 patients with diabetes (389 Chinese, 97 Indians, 89 Malays) in this cross-sectional study between January and May 2008, and the results were subjected to multivariate linear regression analysis.ResultsWe found a significant interaction between FSG and ethnicity on HbAlc. The correlation between FSG and HbAlc among Chinese subjects was 0.25 (95% confidence interval [CI]:0.2-0.3) relative to the Malays (0.38, 95% CI: 0.30-0.45) after adjustment for age; gender; serum creatinine concentrations; body mass index (BMI); duration of diabetes; use of sulfonylureas, metformin, and insulin; and hemoglobin (Hb) and red cell indices (P = .005). Hence, for a given FSG, the predicted HbAlc will be higher in Malays compared to Chinese subjects.We did not observe a statistically significant difference between Indians and Malays with respect to the correlation between FSG and HbAlc.ConclusionWe showed a higher correlation between HbAlc and FSG in Malay subjects relative to the Chinese in this cohort. The ethnic variation in the HbAlc-FSG relationship may be related to differences in percentage contribution by the FSG to overall HbAlc among ethnic groups. Future studies using continuous glucose monitoring (CGM) to elucidate the relative contributions by FSG and postprandial glucose (PPG) to the daily blood glucose profile and the overall HbA1c by ethnicity are required. (Endocr Pract. 2013;19:812-817)