IL-10,IL-6及IL-6受体基因多态性与皮肤黑素瘤易感性的关系

Relationships between Genetic Polymorphisms of Interleukin-10,Interleukin-6,Interleukin-6 Receptor and Patients' Susceptibility to Melanoma

目的探讨白介素10(IL-10)、白介素6(IL-6)及其受体(IL-6R)基因多态性与黑素瘤易感性的关系。方法收集30例黑素瘤患者和30例健康对照者的外周血样本进行基因型分析。对于IL-6及IL-6R,选择11种单核苷酸多态性(SNPs),并且每种SNPs分为杂合子组、纯合子变异体组和野生型组进行分析。对于IL-10,选择-1082(G/A),-819(C/T)和-592(C/A)三个位点的SNPs进行基因型分析。结果在IL-6R基因中发现有4种SNPs(rs6684439,rs4845618,rs4845622,rs8192284)的杂合子组与黑素瘤易感性增高有关(相应的OR及95%CI分别为:1.71,1.12～2.77;1.74,1.04～2.72;1.65,1.05～2.71;1.66,1.06～2.68)。与对照组比较,病例组患者IL-10-1082AA低表达基因型频率明显升高(40.00%vs16.67%;P=0.045;OR=3.33,95%CI1.00～11.14),-1082GA中表达基因型下降(46.67%vs56.67%;P>0.05),-1082GG高表达基因型无明显差异(26.67%vs23.33%;P>0.05)。结论与高表达水平IL-10相关的基因型与黑素瘤易感性无明显相关性,而低表达基因型则可能为危险因子,可能提高黑素瘤易感性;IL-6R可能与黑素瘤易感性增高有关。

Objective To investigate the relationships between genetic polymorphisms of interleukin-10 （IL-10）, interleukin-6 （IL-6）, interleukin-6 receptor （IL-6R） and patients＇ susceptibility to melanoma. Methods Periph- eral blood samples were collected from 30 patients with melanoma （melanoma group） and 30 healthy controls （ control group） , and then were analyzed for genotype. For IL-6 and IL-6R, 11 kinds of single nucleotide polymorphisms （SNPs） were selected, and then each was divided into 3 subgroups： heterozygote group, homozygous variant group, and wild type group. For IL-10, the SNPs of -1082 （G/A）, -819 （C/T）, and -592 （C/ A ） were selected to give genotype analyses. Results Heterozygote groups of 4 kinds of SNPs, which were rs6684439, rs4845618, rs4845622, and rs8192284, in IL-6R gene were discovered to be related to an increase of susceptibility to melanoma. And the corresponding odds ratio （OR） and its 95% confidence interval （95% CI） were 1.71 （1.12-2.77） , 1.74 （1.04 -2.72） , 1.65 （1.05-2.71）, and 1.66 （1.06-2.68）. As compared with control group, frequencies of IL-10 -1082 AA low expression genotype were significantly increased （40.00% vs 16.67% ; P = 0.045; OR = 3.33,95%CI 1.00 - 11.14）, those of -1082 GA median expression genotype were decreased （46.67% vs 56.67% ; P 〉0.05）, and thuose 0f-1082 GG high expression genotype had no significant change （26.67% vs 23.33% ; P 〉 0.05）. Conclusion Genotype, which is related to high expression of IL-10, is not significantly related to susceptibility to melanoma. While low expression of IL-10 related genotype may be a risk factor, and may increase the susceptibility to melanoma. IL-6R may be related to the increase of susceptibility to melanoma.