白介素-16基因多态性与膝骨性关节炎的易感性研究

Association between susceptibility of knee osteoarthritis and genetic polymorphism of interleukin-16

摘要:

目的：探讨汉族人群中白介素-16（interleukin-16，IL-16）基因单核苷酸多态性与膝关节骨性关节炎（knee osteoarthritis，KOA）的相关性。方法：采用“病例-对照”研究方法，纳入150例汉族KOA患者与147例非KOA受试者，其年龄、性别、体质指数相匹配。采用苯酚氯仿法提取外周血白细胞基因组DNA，聚合酶链反应限制性片段长度多态性的方法检测IL-16基因rs11556218、rs4072111和rs4778889 ３个位点与KOA的遗传易感相关性，并用基因测序验证结果。结果：病例组和对照组中3个位点基因型分布均符合Hardy-Weinberg平衡。KOA组rs11556218的T/G基因型频率高于非KOA的人群（OR=2.06，95%CI=1.26～3.35，P=0.005），G/G也明显增加发病风险（OR=2.52，95%CI=1.10～5.74，P=0.005），rs4072111的C/T基因型KOA的发病风险较C/C基因型明显增加（OR=2.45，95%CI=1.42～4.22，P=0.000），T/T也明显增加发病风险（OR=4.04，95%CI=1.06～15.37，P=0.000）；rs11556218与rs4778889存在连锁不平衡关系（D’=0.63，R2=0.236），单倍型TTT增加KOA的发病风险（OR=3.70，95% CI=1.57～8.72，P=0.003），GCC也增加了KOA的发病风险（OR=6.22，95%CI=2.37～16.33，P=0.000）。结论：汉族人群中IL-16基因多态性可能与KOA易感性有关。

Abstract:

Objective：To evaluate the association between the susceptibility of knee osteoarthritis（KOA） and the gene polymorphisms of interleukin-16 in Han population. Methods：A case-control design was employed in this study. A total of 150 patients di－agnosed with primary KOA and 147 controls matched for age，sex and body mass index of Han ancestry were enrolled. Periph－eral blood samples were collected，and the polymerase chain re－action and restriction fragment length polymorphism analysis were used to check the three single nucleotide polymorphisms in the interleukin-16（IL-16）gene. The results were verified by gene sequencing. Results：The genotypes and polymorphisms were distributed in line with the Hardy-Weinberg equilibrium in the case and control groups. The results of non-conditional logistic regression analysis in codominant model showed that T/G genotype（rs11556218） may be a risk factor（OR=2.06；95%CI=1.26 to 3.35；P=0.005），G/G genotype（rs11556218） may be another risk factor（OR=2.52；95%CI=1.10 to 5.74；P=0.005），C/T genotype（rs4072111） may be a risk factor（OR=2.45；95%CI=1.42 to 4.22；P=0.000）and T/T genotype（rs4072111） also increased the risk of KOA（OR=4.04；95%CI=1.06 to 15.37；P=0.000）. Linkage disequilibrium was found between loci rs11556218 and rs4778889（D’=0.63，R2=0.236）. Further stratification analysis by SNPstats based on phenotype showed that TTT may be a risk factor（OR=3.70；95%CI=1.57 to 8.72；P=0.003） and GCC may be another risk factor（OR=6.22；95%CI=2.37 to 16.33；P=0.000）. Conclusion：The genetic polymorphisms of IL-16 gene are one of risk factors associated with the susceptibility of knee osteoarthritis in the Chinese Han population.