Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene.
Linkage studies have mapped loci for diabetic nephropathy and associated phenotypes on chromosome 3q. We studied 14 plausible candidate genes in the linkage region because of their potential role in vascular complications. In a large-scale study of patients from Denmark, Finland, and France who have type 1 diabetes, 1,057 case and 1,127 control subjects, as well as 532 trios, were investigated for association with diabetic nephropathy. We analyzed 69 haplotype-tagging single nucleotide polymorphisms and nonsynonymous variants that were identified by sequencing. Polymorphisms in three genes, glucose transporter 2 (SLC2A2), kininogen (KNG1), and adiponectin (ADIPOQ), showed nominal association with diabetic nephropathy in single-point analysis. The T-allele of SLC2A2_16459CT was associated with a decreased risk of diabetic nephropathy (odds ratio 0.79 [95% CI 0.66-0.96], P = 0.016), whereas the T-allele of KNG_7965CT and the A-allele of ADIPOQ_prom2GA were associated with increased risk of nephropathy (1.17 [1.03-1.32], P = 0.016; 1.46 [1.11-1.93], P = 0.006, respectively). Analyses of the transmission disequilibrium test showed similar trends only for ADIPOQ_prom2GA with the overtransmission of the A-allele to patients with diabetic nephropathy (1.52 [0.86-2.66], P = NS) and of the G-allele to patients without diabetic nephropathy (0.50 [0.27-0.92], P = 0.026). The overall significance for this variant (nominal P = 0.011) suggests that ADIPOQ might be involved in the development of diabetic nephropathy.
Vionnet
Nathalie
N
INSERM U525, Centre National de Génotypage, 2, Rue Gaston Crémieux, 91006 Evry Cedex, France. vionnet@cng.fr
Tregouët
David
D
Kazeem
Gbenga
G
Gut
Ivo
I
Groop
Per-Henrik
PH
Tarnow
Lise
L
Parving
Hans-Henrik
HH
Hadjadj
Samy
S
Forsblom
Carol
C
Farrall
Martin
M
Gauguier
Dominique
D
Cox
Roger
R
Matsuda
Fumihiko
F
Heath
Simon
S
Thévard
Alexandre
A
Rousseau
Rachel
R
Cambien
François
F
Marre
Michel
M
Lathrop
Mark
M
D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003327:Coronary Disease / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D005060:Europe; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012307:Risk Factors; D044465:White People