Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town, South Africa.
PLoS One. 2012;7(12):e52529. doi: 10.1371/journal.pone.0052529. Epub 2012 Dec 20.
Though single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes.
Three SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town. Glomerular filtration rate was estimated (eGFR) and urinary albumin/creatinine ratio (ACR) assessed. Multivariable regressions were used to relate the SNPs with renal traits.
Mean age was 53.6 years, with the expected differences observed in characteristics by diabetic status. Significant associations were found between rs575152 and serum creatinine, and eGFR in the total population, and in diabetic participants (all p≤0.003), but not in non-diabetics (all p≥0.16), with significant interactions by diabetes status (interaction-p≤0.009). The association with ACR was borderline in diabetic participants (p = 0.05) and non-significant in non-diabetics (p = 0.85), with significant interaction (interaction p = 0.02). rs12107 was associated with fasting-, 2-hour glucose and HbA1c in diabetic participants only (interaction-p≤0.003), but not with renal traits.
MYH9 SNPs were associated with renal traits only in diabetic participants in this population. Our findings and other studies suggest that MYH9 may have a broader genetic risk effect on kidney diseases.
尽管非肌肉肌球蛋白基因（MYH9）中的单核苷酸多态性（SNPs）已被报道可解释大多数非糖尿病慢性肾脏病（CKD）的额外风险，但在非裔美国人中，一些研究也表明其与糖尿病终末期肾病有关。我们在一个易患糖尿病的混合血统南非人群中研究了 MYH9 SNPs 与肾脏特征的关联。
使用 Taqman 测定法对来自开普敦贝尔维尔-南部社区的 716 名成年人（198 名患有糖尿病）进行了三种已知与 CKD 相关的 SNPs（rs4821480、rs5756152 和 rs12107）的基因分型。估计肾小球滤过率（eGFR）并评估尿白蛋白/肌酐比（ACR）。使用多变量回归来研究 SNP 与肾脏特征的关系。
平均年龄为 53.6 岁，根据糖尿病状态的不同，观察到特征存在预期差异。rs575152 与血清肌酐和总人群及糖尿病参与者的 eGFR 之间存在显著关联（均 p≤0.003），但在非糖尿病患者中无显著关联（均 p≥0.16），且存在显著的糖尿病状态交互作用（交互作用 p≤0.009）。在糖尿病参与者中，与 ACR 的关联为边缘显著（p = 0.05），而非糖尿病参与者中则无显著关联（p = 0.85），且存在显著的交互作用（交互作用 p = 0.02）。rs12107 仅与糖尿病参与者的空腹、2 小时血糖和 HbA1c 相关（交互作用 p≤0.003），但与肾脏特征无关。
在该人群中，MYH9 SNPs 仅与糖尿病参与者的肾脏特征相关。我们的研究结果和其他研究表明，MYH9 可能对肾脏疾病有更广泛的遗传风险作用。
