Laurent Larifla

Vitamin D deficiency, vitamin D receptor gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes

AIM The prevalence of diabetes in the French West Indies is three times higher than in mainland France. We aimed to assess the associations between vitamin D deficiency, vitamin D receptor (VDR) gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes (T2D). METHODS In this cross-sectional study of 277 patients, 25-hydroxyvitamin D was measured by radioimmunoassay. FokI, BsmI, ApaI and TaqI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. Analysis of covariance and logistic regression were performed. RESULTS The study included 76 patients of Indian descent and 201 patients of African descent. The prevalence of vitamin D deficiency (<20 ng/mL) was 42.6%. When patients were classified into groups with (G1) and without (G2) vitamin D deficiency, there were no significant differences in age, systolic blood pressure, low-density lipoprotein cholesterol and HbA(1c), although body mass index was significantly higher in G1. Vitamin D deficiency was significantly associated with increased diastolic blood pressure and triglyceride levels, and reduced high-density lipoprotein cholesterol (P<0.05). Prevalence of vitamin D deficiency was decreased in patients carrying the f allele of FokI (OR: 0.52; P=0.02) and the aa genotype of ApaI (OR: 0.46; P=0.05). BsmI and TaqI SNPs were not associated with vitamin D deficiency. CONCLUSION The rate of vitamin D deficiency was high in our T2D patients, and was associated with the VDR gene FokI and ApaI polymorphisms and cardiovascular risk profile. Measurements of vitamin D may help to detect T2D patients with cardiovascular risk, and VDR polymorphisms might explain why vitamin D deficiency is so frequently seen in some T2D patients.

Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features

SHBG and liver enzymes levels are both associated with the risk of type 2 diabetes. However, the relationship between SHBG with liver enzymes and intrahepatic fat content remain poorly understood.

Adiponectin gene variants, adiponectin isoforms and cardiometabolic risk in type 2 diabetic patients

The aim of the present study was to examine the associations of rs2241766 (+45T>G), rs1501299 (+276G>T), rs17300539 (−11391G>A) and rs182052 (−10069G>A) in the adiponectin (Ad) gene with adiponectin concentrations, and concomitantly the association of these variants with cardiometabolic risk in type 2 diabetic patients of African ancestry.

Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury.

Influence of Genetic Risk Factors on Coronary Heart Disease Occurrence in Afro-Caribbeans

Background Despite excessive rates of cardiovascular risk factors such as hypertension, diabetes, and obesity, Afro-Caribbeans have lower mortality rates from coronary heart disease (CHD) than do whites. This study evaluated the association of genetic risk markers previously identified in whites and CHD in Afro-Caribbeans. Methods We studied 537 Afro-Caribbean individuals (178 CHD cases and 359 controls) who were genotyped for 19 CHD-related single-nucleotide polymorphisms (SNPs). A genetic risk score (GRS) incorporating the 19 SNPs was calculated. These participants were compared with 1360 white individuals from the Second Northwick Park Heart Study. Results In Afro-Caribbeans, patients with CHD had higher rates of hypertension (78.7% vs 30.1%), hypercholesterolemia (52.8% vs 15.0%), and diabetes (53.9% vs 14.8%) and were more often men (64.0% vs 43.7%) and smokers (27.5% vs 13.4%) compared with non-CHD controls (all P < 0.001). The GRS was higher in Afro-Caribbeans with CHD than in those without CHD (13.90 vs 13.17; P < 0.001) and was significantly associated with CHD after adjustment for cardiovascular risk factors, with an odds ratio of 1.40 (95% confidence interval, 1.09-1.80) per standard deviation change. There were significant differences in allelic distributions between the 2 ethnic groups for 14 of the 19 SNPs. The GRS was substantially lower in Afro-Caribbean controls compared with white controls (13.17 vs 16.59; P < 0.001). Conclusions This study demonstrates that a multilocus GRS composed of 19 SNPs associated with CHD in whites is a strong predictor of the disease in Afro-Caribbeans. The differences in CHD occurrence between Afro-Caribbeans and whites might be a result of significant discrepancies in common gene variant distribution.

High blood pressure and obesity: disparities among four French Overseas Territories.

Background and purpose The epidemiological characteristics of hypertension and obesity in French Overseas Territories (FOTs) have never been compared. Methods This cross-sectional survey included representative population-based samples of 602, 601, 620 and 605 men and women aged more than 15 years, respectively, from four FOTs of Guadeloupe, Martinique, French Guiana, and French Polynesia. Hypertension was defined as blood pressure (BP) at least 140/90 mmHg or the current use of antihypertensive treatment. Results The prevalence of hypertension was 29.2% in Guadeloupe, 17.9% in French Guiana, 27.6% in Martinique and 24.5% in French Polynesia. Considering the Guadeloupe population as the reference group, prevalence of hypertension was significantly lower in French Guiana (P < 0.001), even after controlling for age and sex (P = 0.006). Awareness and treatment of hypertension were similar in French Guiana, Martinique and Guadeloupe (68.8–75.1% and 69.0–73.4%, respectively). Awareness was lower in French Polynesia (50.0%, adjusted P value = 0.04), as was treatment of hypertension (32.4%, adjusted P value = 0.001). Control of hypertension was also lower in French Polynesia (8.8%, adjusted P value = 0.001) compared with the other territories (29.7–31.8%). French Polynesia had the highest prevalence of obesity (33.1%, adjusted P value < 0.001) as compared with the other territories (17.9–22.8%). It had also the largest population attributable fraction of hypertension due to obesity (35.5%) compared with Guadeloupe (13.3%), Martinique (12.3%) and French Guiana (23.6%). Conclusion Wide variations were observed in the prevalence and the management of hypertension between these FOTs, and an especially challenging low control of hypertension was found in French Polynesia. Obesity appears a key target to prevent hypertension, particularly in French Polynesia.

Association of 2238T>C Polymorphism of the Atrial Natriuretic Peptide Gene With Coronary Artery Disease in Afro-Caribbeans With Type 2 Diabetes

BACKGROUND The atrial natriuretic peptide (ANP) is known mainly for its effects on kidney function and blood pressure homeostasis. We investigated the association between two ANP polymorphisms and pre-existing coronary artery disease (CAD) in patients of African descent with type 2 diabetes (T2D). METHODS We conducted a cross-sectional and retrospective study of 218 volunteer Afro-Caribbean patients with T2D. Two polymorphisms (rs5064, 708C>T; and rs5065, 2238T>C) of ANP were genotyped using PCR-restriction fragment length polymorphism analysis. ANCOVA, χ2-test, and logistic regression were used for statistical analysis. RESULTS Among these patients (92 men; 128 women), 67 (30.7%) had CAD, of whom 75% had had myocardial infarction. The frequency of rs5065-C carriers (TC/CC) was significantly lower in patients with CAD than in those without CAD (24 vs. 41%, P = 0.01). The frequency of hypertension did not differ significantly according to genotype. Univariate logistic regression revealed that male sex, age, dyslipidemia, hypertension, and rs5065-C carrier status were associated significantly with CAD. After adjustment for the variables of interest, the odds ratio (ORs) of CAD for rs5065-C carriers (TC/CC) was 0.50 (0.26-0.96; P = 0.038). No association was found between the rs5064 (708C>T) single-nucleotide polymorphisms (SNPs) and pre-existing CAD or cardiovascular risk factors. CONCLUSIONS The ANP rs5065 (2238T>C) C allele seems to exert a protective effect against CAD in T2D patients of African descent. The relevance of ANP polymorphisms for CAD should be determined in different populations.

Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in Non-diabetic adults

BackgroundOur aim was to assess the associations between vitamin D (vitD) status, metabolic profile and polymorphisms in genes involved in the transport (Group-Component: GC) and the hydroxylation (NAD synthetase 1: NADSYN1) of 25 hydroxyvitamin D (25(OH)D) in non-diabetic individuals.MethodsWe conducted a cross-sectional study with 323 individuals recruited from the Health Center of Guadeloupe, France. The rs2282679 T > G and rs2298849 T > C in GC and rs12785878 G > T in NADSYN1 were genotyped.ResultsMean age was 46(range 18–86) years. 57% of participants had vitD insufficiency, 8% had vitD deficiency, 61% were overweight and 58% had dyslipidemia. A higher frequency of overweight was noted in women carrying rs2298849T allele v CC carriers (71% v 50%; P = 0.035). The rs2282679G allele was associated with increased risks of vitD deficiency and vitD insufficiency (OR =3.53, P = 0.008, OR = 2.34, P = 0.02 respectively). The rs2298849 TT genotype was associated with vitD deficiency and overweight (OR =3.4, P = 0.004 and OR = 1.76, P = 0.04 respectively) and the rs12785878 GG genotype with vitD insufficiency and dyslipidemia (OR = 1.80, P = 0.01 and OR = 1.72, P = 0.03 respectively). Based on the number of risk alleles for rs2282679 and rs12785878 combined, a genotype score of 3 (vs. 0–1) was associated with a 5.5 ng/mL average reduction in serum 25(OH)D levels (P = 0.001).ConclusionsThe GC and NADSYN1 genes are associated with the vitamin D status and might contribute to dyslipidemia and overweight independently of 25(OH)D levels.

Gene Polymorphisms of FABP2, ADIPOQ and ANP and Risk of Hypertriglyceridemia and Metabolic Syndrome in Afro-Caribbeans

Objectives The metabolic syndrome (MetS) is a cluster of metabolic abnormalities and cardiovascular risk factors that are highly heritable and polygenic. We investigated the association of allelic variants of three candidate genes, rs1799883-FABP2, rs1501299-ADIPOQ and rs5065-ANP with MetS and its components, individually and in combination, using a genetic risk score. Methods A cross-sectional study was conducted in 462 Afro-Caribbeans subjects without cardiovascular complications or lipid-lowering medications. Cardiovascular risk factors and MetS components (NCEP-ATPIII criteria) were recorded. The 3 SNPs were genotyped. The genetic risk score was calculated by summing the number of risk alleles at each locus. Logistic regressions were used. Results Fifty-eight participants (12.6%) were diabetics and 116 (25.1%) had a MetS. In a dominant model, rs1799883 was associated with hypertriglyceridemia (OR 2.22; P = 0.014) and hypertriglyceridemic waist (HTGW), (P = 0.014) but not significantly with overweight (P = 0.049), abdominal obesity (P = 0.033) and MetS (P = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (P = 0.028) and 2.19 (P = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (P = 0.075). The genetic risk score was significantly associated with MetS. Subjects carrying 4–5 risk alleles (18.8%) had a nearly 2.5-fold-increased risk of MetS compared to those carrying 0–1 risk allele (24.3%): OR 2.31; P = 0.025. Conclusions This study supports the association of FABP2, ANP and ADIPOQ gene variants with MetS or its components in Afro-Caribbeans and suggests a cumulative genetic influence of theses variants on this syndrome and a potential effect on lipid metabolism.

Vitamin D Status, Insulin Resistance, Leptin-To-Adiponectin Ratio in Adolescents: Results of a 1-Year Lifestyle Intervention

AIM: We aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D], insulin resistance and leptin-to-adiponectin (L/A) ratio in Guadeloupean children and adolescents and to analyse the changes in 25(OH)D levels after a 1-year lifestyle intervention program. METHODS: 25(OH)D concentrations were measured via a chemiluminescence assay. Cardiometabolic risk factors, homoeostasis model assessment of insulin resistance (HOMA-IR), and adipokines were measured. The lifestyle intervention included dietary counselling, regular physical activity. RESULTS: Among 117 girls and boys (11–15 years old, 31.6% obese), 40% had vitamin D deficiency (25(OH)D levels < 20 ng/mL). With linear regression models where 25(OH)D and HOMA-IR acted as independent variables and age, sex, BMI, L/A ratio as covariates, 25(OH)D was significantly associated with HOMA-IR alone (P = 0.036). HOMA-IR was also associated with BMI z-score ≥ 2, L/A ratio and an interaction term BMI z-score ≥ 2*L/A ratio (P < 0.001 for all). After one year, in 78 children/adolescent, mean serum 25(OH)D increased significantly from 21.4 ± 4.9 ng/mL at baseline to 23.2 ± 6.0 after 1 year; P = 0.003 whereas BMI z-score, HOMA-IR and L/A ratio decreased significantly (P = 0.003, P < 0.001 and P = 0.012; respectively). CONCLUSION: The association between 25(OH)D and HOMA-IR, independently of obesity and the high prevalence of vitamin D deficiency should be considered in order to prevent the later incidence of T2DM. A healthy lifestyle including non-sedentary and outdoor activities could be a way for improving vitamin D status.