Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
Hum Cell. 2018 Jan;31(1):10-13. doi: 10.1007/s13577-017-0186-6. Epub 2017 Oct 28.
Gout is a multifactorial disease characterized by acute inflammatory arthritis, and it is caused as a consequence of hyperuricemia. A recent meta-analysis of genome-wide association studies has newly identified the relationship between serum uric acid (SUA) levels and rs889472, a single nucleotide polymorphism of musculoaponeurotic fibrosarcoma oncogene (MAF/c-MAF). However, it remained unclear whether rs889472 is associated with gout susceptibility. In the present study, we investigate the association between c-MAF rs889472 and gout in Japanese male population. We genotyped 625 male patients who were clinically diagnosed as gout and 1221 male control subjects without hyperuricemia or a history of gout by TaqMan method. As a result, the major allele (C), which reportedly increases SUA levels, had a higher frequency in the gout cases (58.8%) than in the controls (55.0%). A logistic regression analysis showed a significant association between rs889472 and gout (p = 0.029, odds ratio = 1.17; 95% confidence interval 1.02-1.34). C-MAF is reported as a pivotal transcriptional factor in the development and differentiation of renal proximal tubular cells. Because urate is mainly regulated in renal proximal tubular cells, c-MAF may have an important role in urate regulation in the kidney and influence not only SUA but also gout susceptibility. Our finding shows that rs889472 of c-MAF is associated with gout susceptibility.
痛风是一种多因素疾病,其特征为急性炎症性关节炎,是由于血尿酸升高引起的。最近对全基因组关联研究的荟萃分析新确定了血清尿酸(SUA)水平与肌动蛋白-aponeurotic 纤维肉瘤癌基因(MAF/c-MAF)单核苷酸多态性 rs889472 之间的关系。然而,rs889472 是否与痛风易感性有关仍不清楚。在本研究中,我们调查了 c-MAF rs889472 与日本男性人群痛风之间的关联。我们通过 TaqMan 方法对 625 名临床诊断为痛风的男性患者和 1221 名无高尿酸血症或痛风病史的男性对照进行了基因分型。结果显示,据报道可升高 SUA 水平的主要等位基因(C)在痛风病例(58.8%)中的频率高于对照组(55.0%)。逻辑回归分析显示 rs889472 与痛风之间存在显著关联(p=0.029,优势比=1.17;95%置信区间 1.02-1.34)。c-MAF 被报道为肾近端管状细胞发育和分化的关键转录因子。因为尿酸主要在肾近端管状细胞中调节,c-MAF 可能在肾脏中尿酸调节中起重要作用,不仅影响 SUA,还影响痛风易感性。我们的发现表明 c-MAF 的 rs889472 与痛风易感性有关。