BACKGROUND: A single-nucleotide polymorphism (SNP), rs2268388, in the acetyl-coenzyme A carboxylase beta (ACACB) gene is associated with susceptibility to type 2 diabetic nephropathy (T2DN) in Japanese and European-American populations. Whether this association also exists in Chinese patients is unclear. Attempts at replication in small Singaporean and Korean samples were not significant. METHODS: Eight ACACB SNPs were genotyped in 595 subjects with type 2 diabetes mellitus born in Hong Kong or southern China, 295 with advanced T2DN and 300 with long-standing diabetes lacking nephropathy. Association analyses were focused primarily on SNP rs2268388 and secondarily on flanking SNPs and haplotypes. RESULTS: Adjusting for age, gender and diabetes duration, ACACB SNP rs2268388 was significantly associated with advanced T2DN (odds ratio = 2.39; recessive model; P = 0.0129). CONCLUSION: These results in the Chinese replicate the association between T2DN and rs2268388, as seen in Japanese and European Americans. The ACACB gene and attendant alterations in fatty acid oxidation may play important roles in susceptibility to T2DN. Targeting this pathway may provide novel treatment options for the prevention of diabetic nephropathy.
BACKGROUND: A single-nucleotide polymorphism (SNP), rs2268388, in the acetyl-coenzyme A carboxylase beta (ACACB) gene is associated with susceptibility to type 2 diabetic nephropathy (T2DN) in Japanese and European-American populations. Whether this association also exists in Chinese patients is unclear. Attempts at replication in small Singaporean and Korean samples were not significant. METHODS: Eight ACACB SNPs were genotyped in 595 subjects with type 2 diabetes mellitus born in Hong Kong or southern China, 295 with advanced T2DN and 300 with long-standing diabetes lacking nephropathy. Association analyses were focused primarily on SNP rs2268388 and secondarily on flanking SNPs and haplotypes. RESULTS: Adjusting for age, gender and diabetes duration, ACACB SNP rs2268388 was significantly associated with advanced T2DN (odds ratio = 2.39; recessive model; P = 0.0129). CONCLUSION: These results in the Chinese replicate the association between T2DN and rs2268388, as seen in Japanese and European Americans. The ACACB gene and attendant alterations in fatty acid oxidation may play important roles in susceptibility to T2DN. Targeting this pathway may provide novel treatment options for the prevention of diabetic nephropathy.
Authors: T S Leak; P S Perlegas; S G Smith; K L Keene; P J Hicks; C D Langefeld; J C Mychaleckyj; S S Rich; J K Kirk; B I Freedman; D W Bowden; M M Sale Journal: Ann Hum Genet Date: 2009-01-23 Impact factor: 1.670
Authors: Marcus G Pezzolesi; Pisut Katavetin; Masahiko Kure; G David Poznik; Jan Skupien; Josyf C Mychaleckyj; Stephen S Rich; James H Warram; Andrzej S Krolewski Journal: Diabetes Date: 2009-08-03 Impact factor: 9.461
Authors: Lijun Ma; Ashis K Mondal; Mariana Murea; Neeraj K Sharma; Anke Tönjes; Kurt A Langberg; Swapan K Das; Paul W Franks; Peter Kovacs; Peter A Antinozzi; Michael Stumvoll; John S Parks; Steven C Elbein; Barry I Freedman Journal: PLoS One Date: 2011-08-26 Impact factor: 3.240
Authors: Eugene J Barrett; Zhenqi Liu; Mogher Khamaisi; George L King; Ronald Klein; Barbara E K Klein; Timothy M Hughes; Suzanne Craft; Barry I Freedman; Donald W Bowden; Aaron I Vinik; Carolina M Casellini Journal: J Clin Endocrinol Metab Date: 2017-12-01 Impact factor: 5.958