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Paraoxonase 1 192 Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus
Author(s) -
Murata M.,
Maruyama T.,
Suzuki Y.,
Saruta T.,
Ikeda Y.
Publication year - 2004
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 - 10.1111/j.1464-5491.2004.01252.x
Subject(s) - medicine , pon1 , odds ratio , paraoxonase , diabetes mellitus , microangiopathy , endocrinology , retinopathy , gastroenterology , genotype , nephropathy , plasminogen activator , type 2 diabetes , genetics , biology , gene , oxidative stress
Aims To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. Methods We conducted a case‐control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy ( n = 92) and those with microangiopathies ( n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor‐1, fibrinogen, and platelet glycoprotein Ibα. Results There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 ± 8.4 and 49.0 ± 11.4 years, respectively), or duration of diabetes (14.9 ± 4.5 and 14.5 ± 8.4 years, respectively). Among the gene polymorphisms tested, the 192 Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42–6.89, P = 0.0046, Gln/Gln vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30–6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192 Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor‐1, fibrinogen, and platelet glycoprotein Ibα). Conclusions This study suggests that the presence of the 192 Arg‐allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus. Diabet. Med. (2004)