Replication Study for the Association Between Four Loci Identified by a Genome-Wide Association Study on European American Subjects With Type 1 Diabetes and Susceptibility to Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 8; pp. 2075 - 2079
• Main Authors: Maeda, Shiro, Araki, Shin-ichi, Babazono, Tetsuya, Toyoda, Masao, Umezono, Tomoya, Kawai, Koichi, Imanishi, Masahito, Uzu, Takashi, Watada, Hirotaka, Suzuki, Daisuke, Kashiwagi, Atsunori, Iwamoto, Yasuhiko, Kaku, Kohei, Kawamori, Ryuzo, Nakamura, Yusuke
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2010
• Subjects: Age; Asian Continental Ancestry Group - genetics; Associated diseases and complications; Biological and medical sciences; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 13 - genetics; Creatinine; Development and progression; Diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabetic nephropathies; Diabetic Nephropathies - genetics; Diabetic nephropathy; Diabetic retinopathy; Disease; Disease susceptibility; DNA - genetics; DNA - isolation & purification; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Europe - ethnology; European Continental Ancestry Group - genetics; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Hospitals; Humans; Japan - ethnology; Kidneys; Medical sciences; Meta-Analysis as Topic; Minority & ethnic groups; Nephrology. Urinary tract diseases; Polymorphism, Single Nucleotide; Research design; Risk factors; Single nucleotide polymorphisms; United States; Urinary system involvement in other diseases. Miscellaneous; United States; Europe; Japan; Endocrinopathy; Kidney disease; Type 2 diabetes; Human; Immunopathology; Urinary system disease; Autoimmune disease; Metabolic diseases; Japanese; Concomitant disease; Sensitivity; Type 1 diabetes; Diabetic nephropathy; Replication; Genome
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db10-0067

Genetic factors are believed to contribute to the development and progression of diabetic nephropathy. Recently, a genome-wide association study for diabetic nephropathy revealed four novel candidate loci in European American subjects with type 1 diabetes. In this study, we determined the association of the four loci with diabetic nephropathy in Japanese subjects with type 2 diabetes. We genotyped 11 singlenucleotide polymorphisms (SNPs) in four distinct loci (rs39059 and rs39075 in the CPVL/CHN2, rs1888747 and rs10868025 in FRMD3, rs739401 and rs451041 in CARS, and rs1041466, rs1411766, rs6492208, rs7989848, and rs9521445 in a chromosome 13q locus) in four independent Japanese populations. Six SNPs were nominally associated with diabetic nephropathy in one of the four Japanese populations (P < 0.05; rs451041 in study 1; rs39059 and rs1888747 in study 3; rs1411766 in studies 1 and 4; and rs7989848 and rs9521445 in study 4); however, no significant association was observed for any SNP after correction for multiple testing errors in the individual populations. Nevertheless, a meta-analysis performed for the data obtained from all four populations revealed that one SNP (rs1411766) in chromosome 13q was significantly associated with diabetic nephropathy in the Japanese populations (nominal P = 0.004, corrected P = 0.04, odds ratio 1.26 [95% CI = 1.07-1.47]). Our results suggest that the rs1411766 locus may be commonly involved in conferring susceptibility to diabetic nephropathy among subjects with type 1 or type 2 diabetes across different ethnic groups.