Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans
Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans
复制标题
DOI：
10.1093/ndt/gfr522
复制
发表时间：
2012-04-01
影响因子：
6.1
通讯作者：
Bowden, Donald W.
中科院分区：
文献类型：
--
作者：
Cooke, Jessica N.;Bostrom, Meredith A.;Bowden, Donald W.
背景。非肌肉肌球蛋白IIA基因（MYH9）多态性与非裔美国人和欧裔美国人的局灶节段性肾小球硬化（FSGS）和非糖尿病终末期肾病（ESRD）有关。我们检测了MYH9基因单核苷酸多态性（snp）与欧洲裔美国人T2DM-ESRD的关联；此外，还对3个APOL1基因变异进行了评估。对1963年欧洲裔美国人、536例T2DM- esrd患者和1427例非肾病对照（467例T2DM患者和960例非糖尿病患者）进行了15个MYH9 snp和2个APOL1 snp加6 bp缺失的基因分型。将T2DM- esrd病例与467例T2DM非肾病对照进行比较，发现snp rs4821480、rs2032487和rs4281481构成部分MYH9 E1主要风险单倍型的单变相关性趋于显著[p值0.053-0.055，隐性优势比（OR） 6.08-6.14]。将T2DM-ESRD病例与所有1427例非肾病对照进行比较，我们证实了这三个SNP以及第四个E1 SNP （rs3752462）之间存在关联的证据（p值0.017-0.035,OR 1.41-3.72）。APOL1 G1/G2肾病风险变异在欧美血统的个体中很少见，在T2DM-ESRD患者中存在0.28%的染色体，在对照组中存在0.32%。MYH9 snp rs4821480、rs2032487、rs4281481和rs3752462与欧美人T2DM-ESRD易感性相关。在T2DM-ESRD患者中，APOL1风险变异的出现频率并不明显。因此，MYH9的多态性似乎影响了该样本中肾病的风险。
Background. Polymorphisms in the non-muscle myosin IIA gene (MYH9) are associated with focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease (ESRD) in African Americans and FSGS in European Americans. We tested for association of single nucleotide polymorphisms (SNPs) in MYH9 with T2DM-ESRD in European Americans; additionally, three APOL1 gene variants were evaluated.Methods. Fifteen MYH9 SNPs and two APOL1 SNPs plus a 6-bp deletion were genotyped in 1963 European Americans, 536 cases with T2DM-ESRD and 1427 non-nephropathy controls (467 with T2DM and 960 without diabetes).Results. Comparing T2DM-ESRD cases with the 467 T2DM non-nephropathy controls, single variant associations trending toward significance were detected with SNPs rs4821480, rs2032487 and rs4281481 comprising part of the major MYH9 E1 risk haplotype [P-values 0.053-0.055 recessive, odds ratio (OR) 6.08-6.14]. Comparing T2DM-ESRD cases to all 1427 non-nephropathy controls, we confirmed evidence of association in these three SNPs as well as in the fourth E1 SNP (rs3752462) (P-values 0.017-0.035, OR 1.41-3.72). APOL1 G1/G2 nephropathy risk variants were rare in individuals of European American heritage, present in 0.28% of chromosomes in T2DM-ESRD cases and 0.32% of controls.Conclusions. MYH9 SNPs rs4821480, rs2032487, rs4281481 and rs3752462 are associated with T2DM-ESRD susceptibility in European Americans. The APOL1 risk variants are not present at appreciable frequency in this cohort with T2DM-ESRD. Therefore, polymorphisms in MYH9 appear to influence nephropathy risk in this sample.