title: 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.
abstract: 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.
authors.affiliation: INSERM U525, Centre National de Génotypage, 2, Rue Gaston Crémieux, 91006 Evry Cedex, France. vionnet@cng.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vionnet
authors.forename: David
authors.initials: D
authors.lastname: Tregouët
authors.forename: Gbenga
authors.initials: G
authors.lastname: Kazeem
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Roger
authors.initials: R
authors.lastname: Cox
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Alexandre
authors.initials: A
authors.lastname: Thévard
authors.forename: Rachel
authors.initials: R
authors.lastname: Rousseau
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
mesh_terms: 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