Ancestral origin of variation in the triosephosphate isomerase gene promoter

A high frequency of nucleotide substitutions -5A/G, -8G/A, -24T/G in the triosephosphate isomerase (TPI) gene promoter has been demonstrated in African-Americans. The biological significance of these promoter variants, two of which, -8G/A and -24T/G, occur within regulatory elements essential for transcription, is controversial. The geographical distribution and frequency of allelic variation in the TPI promoter was determined in 378 unrelated normal subjects from Sub-Saharan African (n = 103), Caribbean (n = 26), Northern European (n = 57), Mediterranean (n = 55), Middle Eastern (n = 42), Asian Indian (n = 48) and Oriental (n = 47) populations. Five haplotypes were identified: the common haplotype, -5A-8G-24T, -5G, -8A, -5G-8A, and -5G-8A-24G. All, with the exception of the -8A haplotype, were present in geographically dispersed populations. The -5G allele, which was found at varying frequency in the African, Caribbean and Oriental populations. Phylogenetic comparison suggests this may represent the ancestral promoter haplotype. Homozygosity for the -5G-8A haplotype identified in four subjects confirms that these variants are not responsible for a null allele as formerly postulated. Linkage disequilibrium between related TPI promoter haplotypes, -5G, -5G-8A and -5G-8A-24G, and a single nucleotide polymorphism at nt2262 of the TPI gene supports a single ancestral origin for these mutations which preceeds the separation of African populations.(Au)

Ethnicity and other characteristics predictive of coronary heart disease in a developing community; principal results of the St. James survey, Trinidad

A ten year community survey was undertaken to investigate the high coronary heart (CHI) incidence among people of Indian (South Asian) descent in Trinidad, West Indies. Of 2491 individuals aged 35-69, 2215 (89 percent) were examined and 2069 (83 percent) found to be clinically free of CHD at baseline. After exclusion of 71 of minority ethnic groups, 786 African, 598 Indian, 147 European and 467 adults of mixed descent were followed for CHD morbidity and mortality. In both sexes, adults of Indian origin had higher prevalence rates of diabetes mellitus, a low concentration of high density lipoprotein(HDL) cholesterol, and recent abstinence from alcohol than other ethnic groups. Indian men also had larger skinfold thicknesses than other men. In participants free of CHD at entry, the age-adjusted relative risk of a cardiac event believed due to CHD, was at least twice as high in Indian men and women as in other ethnic groups. In men, blood pressure, diabetes mellitus and low-density lipoprotein(LDL) cholesterol concentration were positively and independently related to risk of CHD, wheras alcohol consumption and HDL cholesterol concentration were inversely associated with risk after allowing for age and ethnic group. The ethnic contrast in CHD persisted when these characteristics were taken into account. In the smaller sample of women, only ethnic groups were predictive of CHD as defined. The failure of point estimates of risk to explain the high CHD incidence in Indians calls for focus on age of onset of risk and examination of other potential risk factors such as insulin concentration. (AU)