title: An intergenic region on chromosome 13q33.3 is associated with the susceptibility to kidney disease in type 1 and 2 diabetes.
abstract: A genome-wide association scan of the Genetics of Kidneys in Diabetes (GoKinD) collections identified four novel susceptibility loci, located on chromosomes 7p14.3, 9q21.32, 11p15.4, and 13q33.3 associated with type 1 diabetic nephropathy. A recent evaluation of these loci in Japanese patients with type 2 diabetes supported an association at the 13q33.3 locus. To follow up these findings, we determined whether single-nucleotide polymorphisms (SNPs) at these same four loci were associated with diabetic nephropathy in the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes collection. A total of 6 SNPs across these loci were genotyped in 646 normoalbuminuric controls and in 743 nephropathy patients of European ancestry. A significant association was identified at the 13q33.3 locus (rs9521445: P = 4.4 × 10(-3)). At this same locus, rs1411766 was also significantly associated with type 2 diabetic nephropathy (P = 0.03). Meta-analysis of these data with those of the Japanese and GoKinD collections significantly improved the strength of the association (P = 9.7 × 10(-9)). In addition, there was a significant association at the 11p15.4 locus (rs451041: P = 0.02). Thus, associations identified in the GoKinD collections on chromosomes 11p15.4 (near the CARS gene) and 13q33.3 (within an intergenic region between MYO16 and IRS2) are susceptibility loci of kidney disease common to both type 1 and 2 diabetes.
authors.affiliation: Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Marcus G
authors.initials: MG
authors.lastname: Pezzolesi
authors.forename: G David
authors.initials: GD
authors.lastname: Poznik
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Adam M
authors.initials: AM
authors.lastname: Smiles
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: James H
authors.initials: JH
authors.lastname: Warram
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D021901:DNA, Intergenic