Plasma factor VII activity (factor VIIc) is one of the independent risk factors for coronary artery disease and is controlled by both genetic and environmental factors. Several studies in healthy Caucasian subjects have revealed an association of a common genetic polymorphism at residue 353 (Arg-»-Gln) of the factor VII gene with plasma factor VIIc. We have investigated the influence of this polymorphism (factor VII Arg/Gln^) on fasting plasma factor VIIc and antigen (factor Vllag) levels and its interaction with triglyceride levels in 185 healthy Dravidian Indians of both sexes (128 men, 57 women). The frequency of Gln 353 has been found to be significantly higher in Dravidian Indians (0.29; confidence interval, 0.27 to 0.30) than in Caucasians (0.10). The distribu-F actor VII is one of the vitamin K-dependent coagulation factors synthesized principally in the liver and secreted as a single-chain glycoprotein of M T 48 000.J It is present in the plasma of healthy adults in a concentration of approximately 450 ng/mL with a half-life of approximately 5 hours. 2^ The active form (factor Vila) is formed by limited proteolysis in the form of two polypeptide chains held together by a disulfide bond. Factor Vila is present in plasma in low concentrations (approximately 1% of factor VII antigen [factor Vllag]) with a half-life of approximately 150 minutes. -5 The cleavage of factor VII to factor Vila is effected by several activated coagulation factors (Xlla, IXa, Xa) and thrombin. Factor Vila binds to tissue factor, and this complex, in the presence of Ca 2+ and phospholipid, converts factor X to factor Xa. Factor VII activity (factor VIIc) has been shown to be an independent risk factor for the development and/or progression of coronary artery disease. 712 However, the Progetto Lambardo Anti-Thrombosis (PLAT) Study and some other studies could not confirm the significance of factor VIIc in cardiovascular disease. 1313 Older and young healthy subjects with a family history of coronary artery disease have been found to have higher factor VIIc compared with those without such a family history. 1618 Another factor is that factor VIIc always

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at -75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24-0.31] than that reported in Caucasians (0.12; 95% CI 0.09-0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits.

233 Pushtoons (129 males and 104 females), 51 Punjabi Muslims (29 males and 22 females) and 21 Afghans (15 males and 6 females) were screened for the presence of red cell glucose-6-phosphate dehydrogenase (G6PD) variants by a dye decolouration screening test and starch gel electrophoresis. The overall frequency of G6PD deficiency in males was found to be about 10%. 17 male G6PD-deficient samples were further investigated for the C→T substitution at nucleotide (nt) 563 (the Mediterranean mutation) and the C→T substitution at nt 1311 (the ‘silent’ allele) of the G6PD gene by PCR amplification followed by digestion with appropriate restriction enzymes. 10 of the 13 Pushtoon, 2 Punjabi and 1 Afghan males had the 563 mutations. Only 1 (Punjabi) out of 13 G6PD-deficient males with the 563 mutation had the silent mutation at nt 1311. The frequency of the silent mutation was found to be about 0.20 in the 60 Pushtoon and 19 Punjabi non-deficient males.

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>Gwith Lp(a) in Malays, and TC, low-density lipoproteincholesterol (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.

as a result of population-specific intronic sequences that predispose individuals to preferential deletion breakpoints.