Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations.
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.
Meirhaeghe
Aline
A
INSERM, U744, Lille, Institut Pasteur de Lille, Lille, Université de Lille 2, UMR-5744, Lille, France. aline.meirhaeghe-hurez@pasteur-lille.fr
Sandhu
Manjinder S
MS
McCarthy
Mark I
MI
de Groote
Pascal
P
Cottel
Dominique
D
Arveiler
Dominique
D
Ferrières
Jean
J
Groves
Christopher J
CJ
Hattersley
Andrew T
AT
Hitman
Graham A
GA
Walker
Mark
M
Wareham
Nicholas J
NJ
Amouyel
Philippe
P
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
D020097:Natriuretic Peptide, Brain; D003596:Cytosine; D013941:Thymine