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 (CKID) 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 chi(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]. P 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.