白细胞介素-6、肿瘤坏死因子-α和基质细胞衍生因子-1基因多态性与糖尿病足溃疡患者血清细胞因子水平的遗传关联

Genetic association of IL-6, TNF-α and SDF-1 polymorphisms with serum cytokine levels in diabetic foot ulcer.

作者信息

Dhamodharan Umapathy, Viswanathan Vijay, Krishnamoorthy Ezhilarasi, Rajaram Rama, Aravindhan Vivekanandhan

机构信息

Department of Biochemistry and Molecular Genetics, Prof M.Viswanathan Diabetes Research Centre, Chennai, India.

出版信息

Gene. 2015 Jul 1;565(1):62-7. doi: 10.1016/j.gene.2015.03.063. Epub 2015 Mar 31.

DOI:10.1016/j.gene.2015.03.063

PMID:25839939

Abstract

The IL-6 -174G/C (rs1800795), TNF-α -308G/A (rs1800629) and -238G/A (rs361525) and SDF-1 801G/A (rs1801157) are well characterized SNPs which have previously been linked to various diabetic complications. However, the involvement of these SNPs in DFU remains poorly studied. In the present study we looked at the association of these SNPs with DFU (disease phenotype) and correlated it with the serum levels of cytokines (intermediate phenotype) along with other clinical risk factors of DFU (adiponectin, leptin and hsCRP). Genotyping was carried out in Normal glucose tolerance ((NGT)/Control=106), T2DM without DFU (T2DM=139), T2DM with neuropathy (DFU-DN=191) and T2DM with PVD (DFU-PVD=79) subjects by PCR-RFLP and the serum cytokine levels were determined by ELISA. IL-6 -176 "C" allele conferred significant protection against T2DM but not against DFU. TNF-α -308 "A" allele (but not -238 SNP) conferred significant susceptibility towards both T2DM and DFU-DN. The SDF-1 "A" allele conferred significant protection against both DM and DFU-DN but not against DFU-PVD. Further, these alleles were shown to influence the serum cytokine/chemokine levels under diabetic conditions. Thus SNPs in cytokine/chemokine genes serve as valuable biomarkers for DFU.

摘要

白细胞介素6（IL-6）-174G/C（rs1800795）、肿瘤坏死因子α（TNF-α）-308G/A（rs1800629）和-238G/A（rs361525）以及基质细胞衍生因子1（SDF-1）801G/A（rs1801157）是特征明确的单核苷酸多态性（SNP），此前已与各种糖尿病并发症相关联。然而，这些SNP在糖尿病足（DFU）中的作用仍研究不足。在本研究中，我们研究了这些SNP与DFU（疾病表型）的关联，并将其与细胞因子的血清水平（中间表型）以及DFU的其他临床风险因素（脂联素、瘦素和高敏C反应蛋白）相关联。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对正常糖耐量（（NGT）/对照组=106）、无DFU的2型糖尿病（T2DM=139）、伴有神经病变的2型糖尿病（DFU-DN=191）和伴有外周血管疾病的2型糖尿病（DFU-PVD=79）受试者进行基因分型，并通过酶联免疫吸附测定（ELISA）测定血清细胞因子水平。IL-6 -176“C”等位基因对2型糖尿病具有显著保护作用，但对DFU无保护作用。TNF-α -308“A”等位基因（而非-238 SNP）对2型糖尿病和DFU-DN均具有显著易感性。SDF-1“A”等位基因对糖尿病和DFU-DN均具有显著保护作用，但对DFU-PVD无保护作用。此外，这些等位基因在糖尿病条件下显示出会影响血清细胞因子/趋化因子水平。因此，细胞因子/趋化因子基因中的SNP可作为DFU的有价值生物标志物。