title: Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations.
abstract: Brain natriuretic peptide (BNP/NPPB) is a member of the natriuretic family involved in the regulation of blood pressure and blood volume as well as lipolysis control in human fat cells. Thus BNP may play a role in energy metabolism and metabolic diseases. We therefore assessed the association between the BNP promoter T-381C polymorphism and risk of type 2 diabetes and metabolic and BNP expression traits in several population samples. In French population-based samples (n = 3216), we found that individuals bearing the -381CC genotype had lower (P = 0.005) fasting glucose levels than -381TC or -381TT individuals. Moreover, the -381CC genotype was less frequent in individuals with type 2 diabetes (n = 280, 13.6%) or with impaired fasting glucose (n = 248, 12.9%) compared with normoglycaemic individuals (n = 2485, 17.8%). The adjusted odds ratio (OR) (95% CI) of type 2 diabetes for -381CC individuals was 0.69 (0.47-1.00), P = 0.05, when compared with -381T allele bearers. We replicated this association in four additional case-control studies for type 2 diabetes. The overall OR (95% CI) of type 2 diabetes was 0.85 (0.76-0.96), P = 0.008, (under a recessive model) (3593 cases and 6646 controls in total). We also found that the -381C allele was associated with higher plasma BNP concentrations (P = 0.015, n = 634) and higher BNP promoter activity in reporter gene assays. Collectively, these data suggest that relatively high BNP expression may protect against type 2 diabetes in humans.
authors.affiliation: INSERM, U744, Lille, Institut Pasteur de Lille, Lille, Université de Lille 2, UMR-5744, Lille, France. aline.meirhaeghe-hurez@pasteur-lille.fr
authors.forename: Aline
authors.initials: A
authors.lastname: Meirhaeghe
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Pascal
authors.initials: P
authors.lastname: de Groote
authors.forename: Dominique
authors.initials: D
authors.lastname: Cottel
authors.forename: Dominique
authors.initials: D
authors.lastname: Arveiler
authors.forename: Jean
authors.initials: J
authors.lastname: Ferrières
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
authors.forename: Mark
authors.initials: M
authors.lastname: Walker
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells; D016022:Case-Control Studies; D002522:Chlorocebus aethiops; D003596:Cytosine; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013941:Thymine
chemical_list: D020097:Natriuretic Peptide, Brain; D003596:Cytosine; D013941:Thymine