The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 × 10−5]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample size

Contribution du système des peptides natriurétiques à la prédisposition génétique au syndrome d'insulino-résistance et au diabète de type 2 dans la population française (études prospectives D.E.S.I.R. et DIABHYCAR)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

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

<div><p>Objectives</p><p>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-<i>FABP2</i>, rs1501299-<i>ADIPOQ</i> and rs5065-<i>ANP</i> with MetS and its components, individually and in combination, using a genetic risk score.</p><p>Methods</p><p>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.</p><p>Results</p><p>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; <i>P</i> = 0.014) and hypertriglyceridemic waist (HTGW), (<i>P</i> = 0.014) but not significantly with overweight (<i>P</i> = 0.049), abdominal obesity (<i>P</i> = 0.033) and MetS (<i>P</i> = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (<i>P</i> = 0.028) and 2.19 (<i>P</i> = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (<i>P</i> = 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; <i>P</i> = 0.025.</p><p>Conclusions</p><p>This study supports the association of <i>FABP2</i>, <i>ANP</i> and <i>ADIPOQ</i> 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.</p></div

Mean genetic risk score, in 415 individuals, according to presence or absence of metabolic syndrome or metabolic syndrome components.

<p>Mean genetic risk score, in 415 individuals, according to presence or absence of metabolic syndrome or metabolic syndrome components.</p

Logistic regressions of overweight and hypertriglyceridemic waist for rs1799883 (<i>FABP2</i>), rs1501299 (<i>ADIPOQ</i>) and rs5065 (<i>NPPA</i>) gene polymorphisms.

<p>Logistic regressions of overweight and hypertriglyceridemic waist for rs1799883 (<i>FABP2</i>), rs1501299 (<i>ADIPOQ</i>) and rs5065 (<i>NPPA</i>) gene polymorphisms.</p

Logistic regressions of metabolic syndrome components and metabolic syndrome for rs1799883 (<i>FABP2</i>), rs1501299 (<i>ADIPOQ</i>) and rs5065 (<i>ANP</i>) gene polymorphisms.

<p>Logistic regressions of metabolic syndrome components and metabolic syndrome for rs1799883 (<i>FABP2</i>), rs1501299 (<i>ADIPOQ</i>) and rs5065 (<i>ANP</i>) gene polymorphisms.</p

Patients’ characteristics according to metabolic syndrome status.

<p>Patients’ characteristics according to metabolic syndrome status.</p

Logistic regression of metabolic syndrome with age, gender, diabetes and the three gene polymorphisms (rs1799883, rs1501299 and rs5065) as covariates.

<p>Logistic regression of metabolic syndrome with age, gender, diabetes and the three gene polymorphisms (rs1799883, rs1501299 and rs5065) as covariates.</p

The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects.

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes