High Prevalence of Rare Monogenic Forms of Obesity in Obese Guadeloupean Afro-Caribbean Children.

Context: The population of Guadeloupe Island exhibits a high prevalence of obesity. Objective: We aimed to investigate whether rare genetic mutations in genes involved in monogenic obesity (or diabetes) might be causal in this population of Afro-Caribbean ancestry. Design and Setting: This was a secondary analysis of a study on obesity conducted in schoolchildren from Guadeloupe in 2013 that aimed to assess changes in children's profiles after a lifestyle intervention program. Through next-generation sequencing, we sequenced coding regions of 59 genes involved in monogenic obesity or diabetes in participants from this study. Participants and Interventions: A total of 25 obese schoolchildren from Guadeloupe were screened for rare mutations (nonsynonymous, splice-site, or insertion/deletion) in 59 genes. Main Outcome Measures: Correlation between phenotypes and mutations of interest. Results: We detected five rare heterozygous mutations in five different children with obesity: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations that were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutations in ABCC8 (p.Lys1521Asn and p.Ala625Val) or KCNJ11 (p.Val13Met and p.Val151Met) that were of uncertain significance. Conclusions: We were able to detect pathogenic or likely pathogenic mutations linked to severe obesity in >15% of this population, which is much higher than what we observed in Europeans (∼5%).

Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans.

OBJECTIVES: Apolipoprotein E gene (APOE) polymorphism is associated with the lipid profile and cardio-vascular disease. However, these relationships vary between ethnic groups. We evaluated, for the first time in an Afro-Caribbean population, the distribution of APOE polymorphisms and their associations with coronary artery disease (CAD), the lipid profile and other cardio-metabolic risk factors. METHODS: We studied 712 Afro-Caribbean subjects including 220 with documented CAD and 492 healthy subjects. TaqMan assays were performed to genotype rs7412 and rs429358, the two variants that determine the APOE alleles ε2, ε3 and ε4. The association between APOE genotype and the lipid profile was analysed by comparing ε2 carriers, ε3 homozygotes and ε4 carriers. RESULTS: The frequencies of ε2, ε3 and ε4 in the overall sample were 8%, 70% and 22%, respectively. CAD was not associated with APOE polymorphism. The total cholesterol level was higher in ε4 carriers compared with ε2 carriers: 5.07 vs 4.59 mmol/L (P = 0.016). The LDL-cholesterol level was lower in APOE ε2 carriers compared with ε3 homozygotes and ε4 carriers: 2.65 vs 3.03 and 3.17 mmol/L, respectively (p = 0.002). The total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios were similar in the three allelic groups. APOE polymorphism was not associated with diabetes, hypertension, waist circumference or body mass index. CONCLUSIONS: Our results indicate that APOE gene polymorphism is associated with the lipid profile but not with CAD in Afro-Caribbean people. This lack of association with CAD may be explained by the low atherogenic profile observed in ε4 carriers, which may warrant further investigation.

Distribution of coronary artery disease severity and risk factors in Afro-Caribbeans.

BACKGROUND: Traditional risk factors are strong predictors of the incidence of coronary artery disease (CAD), but their association with disease severity remains controversial and could differ across ethnic groups. AIMS: In this study, we assessed the prevalence of cardiovascular risk factors (CRFs) in Afro-Caribbean patients with documented CAD, and sought to identify which of these factors are related to disease severity. METHODS: We retrospectively studied 420 consecutive patients with CAD. Disease severity was determined from the results of invasive coronary angiography, based on the presence or absence of multiple (two or three) diseased vessels and the myocardial jeopardy (MJ) score. RESULTS: In the studied population (mean age 64.7 ± 12.4 years), hypertension, diabetes and dyslipidaemia were the most frequent modifiable CRFs, present in 75.9, 47.8 and 37.8% of patients, respectively. Multiple logistic regression analysis showed that diabetes, male sex and personal cardiovascular history significantly increased the risk of multivessel CAD: odds ratios (ORs) of 1.53 (1.01-2.33; P=0.048), 1.61 (1.02-2.55; P=0.043) and 1.68 (1.11-2.56; P=0.015), respectively. Obesity was an independent negative predictor, with an OR of 0.48 (0.29-0.79; P=0.004). Other traditional CRFs (hypertension, dyslipidaemia, smoking, age and family history of vascular disease) were not associated with CAD severity. For high-risk lesions (MJ score ≥8), both diabetes and hypertension were independent predictors of disease severity, whereas obesity was no longer a protective factor. CONCLUSION: Diabetes emerged as the strongest modifiable risk factor predictor of multivessel disease in Afro-Caribbean patients, whereas obesity was an independent protective factor. The underlying mechanisms of these associations should be relevant to disease prevention.