Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Preston Institute of Nano Science and Technology (PINSAT), Preston University, Islamabad, 44000, Pakistan.
Mol Biol Rep. 2019 Jun;46(3):2657-2663. doi: 10.1007/s11033-019-04673-2. Epub 2019 Mar 22.
Osteoarthritis (OA) is a serious health concern globally and is recognized by degradation of articular cartilage, bone remodeling and synovial inflammation. Resistin is an adipokine that shown to be involved in inflammatory process associated with OA. Aim of the current study was to estimate the link of resistin gene polymorphisms (- 420 C>G, + 299 G>A) with genetic susceptibility of knee OA in a Pakistani population. 280 patients and 308 age and sex matched controls were recruited in this case-control study. Genotype and allele frequencies were evaluated by Polymerase chain reaction-Restriction Fragment Length Polymorphism. Resistin concentration was measured by immunoassay. A significant difference in allele and genotype frequency was observed for both study groups. Resistin - 420 mutant genotype was associated with an increased susceptibility to OA (p = 0.001). Similarly, resistin + 299 GA + AA genotypes showed a relation with an elevated risk of knee OA compared to GG genotype (p = 0.01). Moreover, the mutant alleles frequency was significantly high in patient group as compared to healthy individuals for both loci (p < 0.01). Resistin - 420/+ 299 alleles haplotype analysis demonstrated that mutant alleles were more prevalent in OA affected individuals compared to healthy subjects (p < 0.05). The serum resistin levels were not remarkably different in patient vs. control group (p = 0.9). Further, the circulating resistin level was not found to be influenced by - 420G and + 299A alleles and non significant differences were observed in resistin concentration in mutant vs. wild type genotypes for both SNPs (p > 0.05). Our data suggest an association between investigated resistin genetic variants and knee OA susceptibility in our population. This is the first report to show association between investigated single nucleotide polymorphisms and OA among any population.
骨关节炎（OA）是全球范围内一个严重的健康问题，其特征为关节软骨降解、骨重塑和滑膜炎症。抵抗素是一种脂肪细胞因子，其与 OA 相关的炎症过程有关。本研究旨在评估抵抗素基因多态性（-420C>G、+299G>A）与巴基斯坦人群膝关节 OA 的遗传易感性之间的关系。在这项病例对照研究中，共招募了 280 名患者和 308 名年龄和性别匹配的对照者。通过聚合酶链反应-限制性片段长度多态性评估基因型和等位基因频率。通过免疫测定法测量抵抗素浓度。两组研究对象的等位基因和基因型频率均存在显著差异。抵抗素-420 突变基因型与 OA 易感性增加相关（p=0.001）。同样，与 GG 基因型相比，抵抗素+299GA+AA 基因型与膝关节 OA 的风险升高有关（p=0.01）。此外，两个基因座的突变等位基因频率在患者组中明显高于健康个体（p<0.01）。抵抗素-420/+299 等位基因单倍型分析表明，与健康受试者相比，突变等位基因在 OA 患者中更为常见（p<0.05）。与对照组相比，患者组的血清抵抗素水平无明显差异（p=0.9）。此外，未发现 -420G 和 +299A 等位基因对循环抵抗素水平有影响，两个 SNP 的突变型与野生型基因型之间的抵抗素浓度无显著差异（p>0.05）。我们的数据表明，在所研究的人群中，抵抗素遗传变异与膝关节 OA 易感性之间存在关联。这是第一项表明在所研究的单核苷酸多态性与 OA 之间存在关联的报告。
