A candidate gene approach to genetic contributors to the development of IgA nephropathy.

BACKGROUND:Genetic factors contributing to the development of IgA nephropathy remain to be elucidated. METHODS:The present multicenter cross-sectional case-control study measured genotype frequencies of 65 atherosclerotic disease-related gene polymorphisms in 230 Japanese patients with IgA nephropathy and 262 apparently healthy volunteers with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and negative or trace proteinuria and hematuria by dipstick test [non-chronic kidney disease (CKD) participants]. Clinical characteristics at kidney biopsy of patients with IgA nephropathy and those at the study recruitment of non-CKD participants were included as covariates in multivariate logistic regression models. RESULTS:Among 31 gene polymorphisms with ≥5% of minor genotype in non-CKD participants, methionine synthase MTR A2756G (D919G) was significantly associated with IgA nephropathy using χ(2) test even after controlling for family-wise error rate by the method of Bonferroni (P = 0.044). A multivariate nonconditional logistic regression model identified MTR A2756G as a significant contributor of IgA nephropathy [2756AG and GG versus AA, odds ratio 0.42 (95% confidence interval 0.25-0.69) and 0.21 (95% confidence interval 0.06-0.68), P(trend) < 0.001]. After each patient with IgA nephropathy was randomly matched to a non-CKD participant on age (±5 years), gender, mean arterial pressure (±5 mmHg) and eGFR (±5 mL/min/1.73 m(2)), a multivariate conditional logistic regression model also verified their significant association [odds ratio 0.42 (95% confidence interval 0.18-1.00) and odds ratio 0.09 (95% confidence interval 0.01-0.73), P(trend) = 0.004]. MTR A2756G was not associated with slope of eGFR (mL/min/1.73 m(2)/year) in 230 patients with IgA nephropathy. CONCLUSION:MTR A2756G was associated with the development, but not progression, of IgA nephropathy.

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