KCNQ1 SNPS and susceptibility to diabetic nephropathy in East Asians with type 2 diabetes
KCNQ1 SNPS and susceptibility to diabetic nephropathy in East Asians with type 2 diabetes
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DOI：
10.1007/s00125-012-2602-5
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发表时间：
2012-09-01
期刊：
影响因子：
8.2
通讯作者：
Ng, D. P. K.
中科院分区：
文献类型：
--
作者：
Lim, X. L.;Nurbaya, S.;Ng, D. P. K.
日本的一项研究早些时候报道，KCNQ 1单核苷酸多态性（SNPs）可能与糖尿病肾病有关。为了进一步研究这一发现，我们分析了居住在新加坡的中国2型糖尿病患者中KCNQ 1基因座内的三个SNP rs 2237895、rs 2237897和rs 2283228与蛋白尿的关联。蛋白尿分为分类性（微量蛋白尿和大量蛋白尿）和连续性（log（e）白蛋白/肌酐比值[ACR]）两类。使用点尿样本通过ACR测定白蛋白尿，并使用估计的GFR估算肾功能。适当时，使用invader和Taqman试验进行基因分型。多变量回归分析用于分析SNPs与肾脏性状之间的关联，在多重假设检验和调整潜在混杂因素后，检测到rs 2283228与大量白蛋白尿（p <0.001，校正p < 0.01）以及log（e）ACR（p = 0.004，校正p = 0.036）之间存在显著关联。随着糖尿病肾病严重程度的增加（低和高微量白蛋白尿，大量白蛋白尿），观察到OR增加的趋势。rs 2237897，先前在早期的日本研究中涉及，也与大量白蛋白尿有关，但在多次检测校正后，这一发现并不显著。对中国和日本研究的荟萃分析显示，这两个SNPs与大量白蛋白尿显著相关，与之前的日本研究一起，我们的研究结果支持了这样一个假设，即除了KCNQ 1是一个确定的2型糖尿病基因外，该基因的遗传变异可能有助于东亚人糖尿病肾病的易感性。
A Japanese study had earlier reported that KCNQ1 single-nucleotide polymorphisms (SNPs) may be associated with diabetic nephropathy. To further investigate this finding, we analysed three SNPs, rs2237895, rs2237897 and rs2283228, within the KCNQ1 locus for association with albuminuria among Chinese type 2 diabetic patients residing in Singapore. Albuminuria was analysed as both categorical (micro- and macroalbuminuria) and continuous traits (log (e) albumin/creatinine ratio [ACR]).A total of 752 Chinese patients with type 2 diabetes were included in the study. Albuminuria was determined by ACR using spot urine samples, and renal function was approximated using estimated GFR. Genotyping was performed using invader and Taqman assays as appropriate. Multivariate regression analyses were used to analyse the associations between SNPs and renal traits.Significant associations were detected between rs2283228 and macroalbuminuria (p < 0.001, corrected p < 0.01), as well as log (e) ACR (p = 0.004, corrected p = 0.036) after multiple hypothesis testing and adjustment for potential confounding. A trend of increasing OR was observed with increasing severity of diabetic nephropathy (low and high microalbuminuria, macroalbuminuria). rs2237897, previously implicated in the earlier Japanese study, was also associated with macroalbuminuria, but this finding did not remain significant after correction for multiple testing. Meta-analyses of the Chinese and Japanese studies revealed both SNPs to be significantly associated with macroalbuminuria.Together with the previous Japanese study, our findings support the hypothesis that, in addition to KCNQ1 being an established type 2 diabetes gene, genetic variation in this gene may contribute to susceptibility to diabetic nephropathy in East Asians.