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Diabetic nephropathy is associated with the 5¢‐end dinucleotide repeat polymorphism of the aldose reductase gene in Chinese subjects with Type 2 diabetes
Author(s) -
Liu Y. F.,
Wat N. M. S.,
Chung S. S. M.,
Ko B. C. B.,
Lam K. S. L.
Publication year - 2002
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.1464-5491.2002.00632.x
Subject(s) - microalbuminuria , medicine , diabetic nephropathy , albuminuria , genotype , endocrinology , aldose reductase , odds ratio , nephropathy , diabetes mellitus , allele , allele frequency , proteinuria , genetics , biology , gene , kidney
Aims We investigated whether the promoter dinucleotide repeat polymorphism of the aldose reductase gene (5′‐ALR2), implicated in the development of nephropathy in Type 1 diabetes, was associated with diabetic nephropathy in Type 2 diabetes. Methods In 265 Southern Chinese with Type 2 diabetes the 5′‐ALR2 polymorphism was identified in genomic DNA using polymerase chain reaction and automated fluorescent scanning. They were classified as normoalbuminuric ( n = 128), microalbuminuric ( n = 85) or albuminuric ( n = 52) according to the mean albumin excretion rate of two 12‐h overnight collections. Results The 5′‐ALR2 allele and genotype distributions differed significantly among the three groups of patients ( P < 0.003 and P < 0.01, respectively). Normoalbuminuric patients had the lowest Z − 2 allele frequency: 17.6% vs. 28.2% and 23.1% for microalbuminuric and albuminuric patients, respectively, and the highest Z + 2 allele frequency: 36.7% vs. 21.2% and 23.1% in microalbuminuric and albuminuric patients, respectively. They also had the lowest Z − 2/X genotype frequency (X = any allele other than Z + 2): 18.8% vs. 36.5% in microalbuminuric ( P < 0.01) and 38.5% in albuminuric patients ( P < 0.02), respectively, but the highest Z + 2/Y genotype frequency (Y = any allele other than Z − 2): 50.7% vs. 27.0% and 34.6% in microalbuminuric ( P < 0.001) and albuminuric patients, respectively. In a multiple logistic regression model, the Z − 2/X genotype (odds ratio 3.10; P < 0.025) was an independent risk factor of diabetic nephropathy, microalbuminuria or albuminuria, together with age, mean arterial pressure and body mass index. Conclusions The 5′‐ALR2 dinucleotide repeat polymorphism is associated with the development of diabetic nephropathy in Southern Chinese with Type 2 diabetes. Diabet. Med. 19, 113–118 (2002)