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

作者：Yamamoto Ryohei; Nagasawa Yasuyuki^*; Shoji Tatsuya; Katakami Naoto; Ohtoshi Kentaro; Hayaishi Okano Rieko; Yamasaki Yoshimitsu; Yamauchi Atsushi; Tsubakihara Yoshiharu; Imai Enyu; Rakugi Hiromi; Isaka Yoshitaka

来源：Nephrology Dialysis Transplantation, 2012, 27(3): 1020-1030.

DOI：10.1093/ndt/gfr369

• gene polymorphism
• IgA nephropathy
• methionine synthase MTR A2756G (D919G)

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.

• 出版日期2012-3