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.     

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.     

Glutamate-pyruvate transaminase subtypes in Singapore ethnic groups

Autopsy liver samples from 244 Chinese, 119 Malays and 136 Indians were screened for glutamate-pyruvate transaminase (GPT) subtypes by starch-gel electrophoresis and isoelectric focusing at pH 5-7. Altogether, ten phenotypes controlled by four alleles (GPT1, GPT2A, GPT2B and GPT3) were identified. There was no significant difference in the frequency of GPT alleles between the ethnic groups. The distribution of GPT types was in agreement with the Hardy-Weinberg equilibrium in all the ethnic groups.     

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.     

<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.     

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.     

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.     

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.     

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.     

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.     

Tissue-type plasminogen activator restriction fragment length polymorphism in the Chinese, Indians and Malays of Singapore

A total of 215 subjects comprising 95 Chinese, 66 Malays and 54 Indians were investigated for restriction fragment length polymorphisms of the tissue-type plasminogen activator (PLAT) gene at an EcoRI site using the probe ptPA-4352. The phenotypic distribution showed a good agreement with the Hardy-Weinberg equilibrium. The gene frequencies of PLAT*1 were found to be 0.47 in the Chinese, 0.52 in the Malays and 0.41 in South Indians.     

Restriction fragment length polymorphism (RFLP) at the DNF15S2 locus in three ethnic groups of Singapore

Three different ethnic groups from Singapore comprising 79 Chinese, 34 Malays and 23 Indians of Dravidian origin, were investigated for the HindIII RFLP at the DNF15S2 locus. The three populations had very similar allele frequencies and the frequency of rarer(S) allele was significantly (p less than 0.01) lower (0.21) in these ethnic groups compared to that in Caucasians (0.41). The phenotypic distributions were at Hardy-Weinberg equilibrium.     

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.     

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.     

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.     

Distribution of red cell phosphoglucomutase-1 subtypes in several Mongoloid populations of East Asia

The distribution of red cell phosphoglucomutase (PGM) subtypes was determined by starch-gel electrophoresis and isoelectric focusing in a group of 2,484 unrelated individuals from ten Mongoloid populations of East Asia. The sample comprised 998 Chinese from various localities--Singapore, 325; Malaysia, 270; Taiwan, 276; Hong Kong, 67; Fouzhou, 60--as well as 342 Koreans; 252 Filipinos; 529 Thais; 336 Malays, and 27 Indonesians. Altogether 15 phenotypes controlled by four common and five rare alleles at the PGM1 locus were observed in these populations. The frequency of the most frequent allele (PGM1+) varied from 0.56 to 0.74, with the highest frequency observed in the Singapore Chinese and the lowest in the Malays. Within the Chinese from different localities a significant degree of heterogeneity was observed at the PGM1 locus. The rare allele (PGM17)6 was observed only among the Chinese, Thais, and Malays, while the PGM1 was lacking in the Filipinos. A new allele with ahigh pI (6.5) was observed in a low frequency in all the populations but the Malays.     

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.     

Continuing fertility transitions in a plural society: ethnic trends and differentials in Peninsular Malaysia

Fertility in Peninsular Malaysia has declined continuously from the late 1950s, reaching a total fertility rate of 3735 in 1983. All ethnic groups in Malaysia have contributed to this modern demographic transition but the rate of change has been most rapid for Chinese and Indians, Malay fertility having reached a plateau in the early 1980s. The effect of age structure, marital patterns and marital fertility (by parity) on the fertility declines for each ethnic community are analyzed. There has been a tendency, in each ethnic group, for the age distribution within the group of reproductive-age women to grow younger, reflecting the entry into the younger reproductive ages of the large birth cohorts of the 1950s and early 1960s. The effect of this on crude birth rates is hard to determine, because rising age at marriage and increasing use of contraception meant that fertility was increasingly concentrated in the more central reproductive ages. By the 1990s, the earlier declines in fertility will bring about a decline in the proportion of the total population made up of females in the main reproductive ages. After that point, further declines in fertility will be reflected in a sharper decline in the crude birth rate and hence the rate of population increase. Between 1947 and 1980, the age at marriage changed dramatically for females of all ethnic groups. The transition to higher age at marriage for Chinese was completed earlier, and since 1970 has risen by only a year. For Malays and Indians, the rise began later, proceeded faster and continued right up to 1980 when the medium ages at 1st marriage were Malays 22, Indians 23, Chinese 24 years. In 1980, Malay women on average were marrying 5 years later, and Indian women 6 years later than had their mothers' generation in 1947. The proportion never-married among Malay and Indian women aged 20-24 rose from 1/10 to 1/2 over this period; relatively greater changes are evident at ages 25-29. Other factors are the almost complete shift from parent-arranged to self-arranged marriages. Family size desired has decreased for all groups and the decline in breastfeeding has been offset by the sharp increase in the practice of contraception. Continuation of these trends would lead to replacement-level fertility for Malaysian Chinese and Indians by the year 2000. Malay fertility is likely to continue to decline but at a more moderate pace.     

Transferrin C subtyping in Malaysians and in Indonesians from North Sumatra

Summary Malays, Chinese, and Indians from Peninsular Malaysia; Ibans and Bidayuh from Sarawak State; Kadazans from Sabah State, Northern Borneo; and Bataks, Minangkabau, and Javanese from North Sumatra, Indonesia, were subtyped for transferrin C by polyacrylamide gel isoelectric focusing. All nine populations studied are polymorphic for two alleles, Tf^C1 and Tf^C2. Tf^C3 was polymorphic in six populations and present as a rare variant in the other three. The frequency of Tf^C1 ranged from 0.855 in Bidayuh to 0.711 in Javanese, that of Tf^C2 from 0.231 in Indians to 0.113 in Bidayuh, and that of Tf^C3 from 0.030 in Javanese and Chinese to 0.008 in Bidayuh. Tf^Dchi is polymorphic in all the populations that we studied except in Minangkabau, in whom it is present as a rare variant, and in Indians, in whom it is absent.     

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.