A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27.

Prevalence of coronary heart disease (CHD), of type 2 diabetes (T2DM) and of the metabolic syndrome are in Mauritius amongst the highest in the world. As T2DM and CHD are closely associated and have both a polygenic basis, we conducted a 10 cM genome scan with 403 microsatellite markers in 99 independent families of North-Eastern Indian origin including 535 individuals. Families were ascertained through a proband with CHD before 52 years of age and additional sibs with myocardial infarction (MI) or T2DM. Model-free two-point and multipoint linkage analysis were performed using the Mapmarker-Sibs (MLS) and maximum-likelihood-binomial (MLB) programs for autosomal markers and the Aspex program for chromosome X markers. In a second step, additional markers were studied to increase the genetic map density in three regions on chromosomes 3, 8 and 16 where initial indication for linkage was found. Our data show suggestive linkage with CHD on chromosome 16p13-pter with the MLS statistics at 8.69 cM (LOD = 3.06, P = 0.00017) which partially overlaps with a high pressure (HBP) peak. At the same locus, a nominal indication for linkage with T2DM was found in 35 large T2DM Pondicherian families also having Indian origin. With respect to region 8q23, we found suggestive linkage with T2DM (LOD = 2.55, P = 0.00058) as well as with HBP. On 3q27, we replicated previous indication for linkage found in Caucasians (for the metabolic syndrome and for diabetes) according to the categorized trait for CHD and MI with the MLB statistics (LOD = 2.13, P = 0.0009). The genome scan also revealed nominal evidence of linkage with CHD on 10q23 (LOD = 2.06, P = 0.00188). Interestingly, we detected in the same region overlapping linkages with three QTLs: age of onset of CHD (LOD = 2.03), HDL cholesterol (LOD = 1.48) and LDL/HDL ratio (LOD = 1.34). Ordered-subset analysis based on family body mass index ranking replicated finding on 2q37 for T2DM (at Calpain 10 locus). These results show the first evidence for susceptibility loci that predispose to CHD, T2DM and HBP in the context of the metabolic syndrome.

Three major G6PD-deficient polymorphic variants identified among the Mauritian population.

We report the results of the first epidemiological study investigating glucose 6-phosphate dehydrogenase (G6PD) deficiency among the heterogenous Mauritian population. Mauritius has a population of approximately 1 million, and of these 66.8% are Indo-Mauritian (of Indian origin), 27.9% are Creoles (of African ancestry) and 2.1% are Sino-Mauritian, predominantly of Chinese origin. Of the 1435 Mauritian males tested, 73 (5.1%) were G6PD deficient. However, the prevalence varied considerably between the two major ethnic groups: 35/1157 (3.0%) for Indo-Mauritians and 37/267 (13.9%) for Creoles. Molecular analysis revealed three major deficient polymorphic variants; G6PD Orissa, G6PD Mediterranean and G6PD A-. G6PD Orissa (nt 131 G-->C; residue 44 Ala-->Gly) was found to be the most common variant among Indo-Mauritians: this deficient variant was recently identified to be highly characteristic of the tribal groups in central India. In Creoles the most common deficient variant was G6PD A- (27/37). These data are consistent with the different ancestral contributions to the present gene pool of the Mauritian population. This study has provided further information as to the precise nature of G6PD deficiency at the molecular level among Indians, about whom previously there was scant information. The data presented suggest that G6PD Orissa is widespread in central and southern states of India. Additionally, the identification and frequency of G6PD-deficient alleles in Mauritius is of public-health importance.