Ng Daniel P K, Nurbaya Siti, Ye Sandra H J, Krolewski Andrzej S
Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine,National University of Singapore, Singapore, Singapore.
Kidney Int. 2008 Aug;74(4):521-7. doi: 10.1038/ki.2008.202. Epub 2008 May 21.
The human chromosome 7p21 locus harbors a major gene that influences variation of glomerular filtration rate and development of end-stage renal disease. The pro-inflammatory IL-6 cytokine is a candidate gene since chronic inflammation has been implicated in diabetic nephropathy and this gene is located under the peak of linkage. To test this, single nucleotide polymorphism (SNP) and haplotype analyses were performed using a case-control study of 295 patients consisting of 138 with proteinuria, 157 with chronic renal failure and these were compared to 174 control patients with normal albumin excretion. Five tagging SNPs were selected for analysis based on linkage disequilibrium patterns and proximity to the functionally important -634G>C SNP in the IL-6 promoter. Initial analysis suggested that a -174G>C polymorphism may be associated with risk of chronic renal failure but this was not significant after Bonferroni correction. While haplotype analyses showed no association with proteinuria; a significant association with chronic renal failure was found. There was significantly more of the GGGAGC haplotype among patients with chronic renal failure compared to controls and this association remained significant even after correction for multiple testing. Our study has found a specific IL-6 haplotype conferring risk for impaired renal function in patients with type 2 diabetes.
人类染色体7p21位点包含一个影响肾小球滤过率变异和终末期肾病发生发展的主要基因。促炎性白细胞介素-6（IL-6）细胞因子是一个候选基因，因为慢性炎症与糖尿病肾病有关，且该基因位于连锁峰值之下。为对此进行验证，采用病例对照研究对295例患者进行了单核苷酸多态性（SNP）和单倍型分析，其中包括138例蛋白尿患者、157例慢性肾衰竭患者，并将这些患者与174例白蛋白排泄正常的对照患者进行比较。基于连锁不平衡模式以及与IL-6启动子中功能重要的-634G>C SNP的接近程度，选择了5个标签SNP进行分析。初步分析表明，-174G>C多态性可能与慢性肾衰竭风险相关，但经Bonferroni校正后并不显著。虽然单倍型分析显示与蛋白尿无关；但发现与慢性肾衰竭存在显著关联。与对照组相比，慢性肾衰竭患者中GGGAGC单倍型明显更多，即使在进行多重检验校正后，这种关联仍然显著。我们的研究发现了一种特定的IL-6单倍型，它会增加2型糖尿病患者肾功能受损的风险。
