Currie D, Maxwell A P, Sadlier D, McKnight A J
Nephrology Research Group, Queen's University of Belfast, Belfast, Northern Ireland, UK.
Diabet Med. 2008 Aug;25(8):1001-5. doi: 10.1111/j.1464-5491.2008.02511.x.
Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene.
Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies.
Chi(2) analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case-control collection negated this association.
We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes.
内收蛋白2（β）（ADD2）是一个生物学和位置候选基因，被认为会增加患糖尿病肾病的遗传风险。本研究旨在全面调查该基因所在基因组区域内所有常见的和可能具有功能的多态性。
通过Sequenom iPLEX和TaqMan技术相结合的方法，对来自不列颠群岛的1467名白人个体（病例718例；对照749例）进行了国际人类基因组单体型图计划（International HapMap Project）第二阶段衍生的标签单核苷酸多态性（23个）和计算机预测的功能变异（2个）的基因分型。
病例组与对照组基因型和等位基因频率的卡方分析显示，在5%的显著水平上有一个变异存在关联的证据较弱（rs10164951，P = 0.02）。在本病例对照研究中进行多重检验校正后，这种关联不复存在。
我们选择了适合ADD2基因遗传研究的合适变异子集，并报告了ADD2基因多态性与糖尿病肾病的首次研究。我们的结果表明，ADD2基因中的常见多态性和可能具有功能的变异对该1型糖尿病白人人群患糖尿病肾病的遗传易感性没有强烈影响。
