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.

Type II (non-insulin-dependent) diabetes mellitus is characterised by insulin resistance, pancreatic betacell defect, hypertension, dyslipidaemia and central obesity, and is recognised as part of a cluster of cardiovascular risk factors generally known as the Metabolic Syndrome [1]. The Indian Ocean island of Mauritius recently provided the background for a longitudinal epidemiological study (1987±1998) which is now seen as an indicator of the potential global impact of Type II diabetes [2,3]. Mauritius has a multiethnic population of 1.2 million, including people of Asian Indian (66 %), mixed European-African-Indian (31 %) and Chinese (3 %) descent. In 1987, the agestandardised prevalence of Type II diabetes in adults aged 30 years or more was 14.3 %, increasing to Diabetologia (2001) Abstract Aims/hypothesis. To measure oxidative stress, endothelial dysfunction and insulin resistance in Indian Mauritians at different stages of development of Type II (non-insulin-dependent) diabetes mellitus. Methods. Plasma total 8-epi-PGF 2a , an indicator of oxidative stress, was determined in age-matched subjects with normal glucose metabolism (n = 39), impaired glucose tolerance (n = 14), newly diagnosed diabetes (n = 8) and established diabetes (n = 14). Plasma glucose and insulin were measured at baseline and 2 h following an oral glucose tolerance test. Endothelial function was assessed by non-invasive digital pulse wave photoplethysmography. Results. Plasma 8-epi-PGF 2a increased in subjects with impaired glucose tolerance (p < 0.05) compared with control subjects, and was even higher in newly diagnosed diabetic patients (p < 0.01) and established (p < 0.01) diabetic patients. A tendency towards reduced endothelial function in subjects with impaired glucose tolerance became significant in patients with newly diagnosed and established diabetes (p < 0.01), and was correlated with 8-epi-PGF 2a (r = 0.36, p < 0.01). Insulin resistance (homeostasis model assessment) did not change in subjects with impaired glucose tolerance compared with control subjects, but increased in newly diagnosed (p < 0.01) and established (p < 0.001) diabetic subjects. The 8-epi-PGF 2a was correlated with fasting glucose (r = 0.50, p < 0.001), triglycerides (r = 0.40, p < 0.001) and insulin resistance (r = 0.35, p < 0.001). Conclusion/interpretation. Oxidant stress is an early event in the evolution of Type II diabetes and could precede the development of endothelial dysfunction and insulin resistance. [Diabetologia (2001) 44: 706± 712

Several studies have documented high rates of coronary heart disease (CHD) among migrants from the Indian subcontinent [1]. The common risk factors shared by these communities are increased plasma triglyceride concentrations, decreased high density lipoprotein (HDL) cholesterol, high fasting and post-glucose insulin concentrations, central obesity and a high prevalence of Type II (non-insulin-dependent) diabetes mellitus. These features, found consistently in Indian communities settled overseas, reflect an underlying state of insulin resistance [2]. The majority of the Mauritian population, 70 %, are descen- Diabetologia (2001) Abstract Aims/hypothesis. Insulin resistance syndrome is an important risk factor for developing premature coronary heart disease. It is a complex syndrome which could arise from the interaction of several genes modulated by environmental factors. The Trp64Arg polymorphism in the b3-adrenoreceptor gene has been found to be associated with insulin resistance, obesity or with earlier onset of Type II (non-insulin-dependent) diabetes mellitus in different populations. We aimed to study whether features of the insulin resistance syndrome are associated with this polymorphism in Indo-Mauritian patients with premature coronary heart disease. Methods. We carried out a case control study using PCR-RFLP techniques, of consecutive Indo-Mauritian patients (n = 338) with premature coronary heart disease (onset below age of 60 years) and unrelated control subjects (n = 148) of the same ethnicity.Results. In Indo-Mauritian patients with premature coronary heart disease who were not treated by beta blockers, triglyceride concentrations were lower (median: 1.44 vs 1.93 mmol/l, p < 0.008) and HDL cholesterol concentrations higher (mean: 0.98 vs 0.85 mmol/l, p < 0.015) in those carrying the wild type of the b3-adrenoreceptor gene than in those carrying the Trp64Arg variant. The latter genotype specific effect on HDL was inverse in patients treated with beta blockers. Conclusion/interpretation. The b3-adrenoreceptor gene variant seems to modulate the effects of beta blockers on triglyceride and HDL cholesterol concentrations in this group of Indo-Mauritian population. Dyslipidaemia, a key component of the metabolic syndrome has a heterogeneous nature in IndoMauritian subjects. This potent risk factor for earlyonset coronary heart disease is influenced by the interaction between genetic and environmental effects.[Diabetologia (2001)

No abstract

Eighty‐five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I‐converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early‐onset MI was found in this population group. Other gene components of the renin‐angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.