白细胞介素28B基因多态性在冷球蛋白阳性与阴性丙型肝炎患者中的比较

The difference of IL-28B polymorphisms between hepatitis C patients with and without cryogiobulinemia

目的探讨冷球蛋白血症慢性丙型肝炎（CHC）患者白细胞介素（IL）28B基因多态性的分布。方法检测62例用聚乙二醇干扰素a-2a联合利巴韦林进行抗病毒治疗的CHC患者血清冷球蛋白性质，并检测IL-28Brs8099917、rsl2979860、rsl2980275的基因型。并分别检测患者血清HCVRNA在基线、治疗后4周与12周、治疗结束、治疗结束后24周时的水平。对计量资料用独立样本t检验或秩和检验进行两组间的比较，对计数资料用X2检验、Fisher’S精确概率法进行组间比较。结果27例患者血清冷球蛋白阳性，发生率为43．5％。IL-28Brs8099917TT基因型（63．0％与94．3％，x2=9．581，P〈0．01）与T等位基因（81．5％与97．1％，X2=8．554，P〈0．01）、IL-28Brsl2979860C等位基因（83．3％与94．3％，X2=3．896，P〈0．05）在冷球蛋白阳性CHC患者中的分布频率低于冷球蛋白阴性患者。结论IL-28B的基因型或等位基因分布在冷球蛋白阳性与阴性CHC患者间存在差异。

Objective To determine whether patients infected with chronic hepatitis C （CHC） show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia. Methods Sixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a （weekly, 180 g, subcutaneous injection） plus ribavirin （daily, 10-15 mg/kg body weight, oral） for 48 weeks, with individualized dosage adjustments according to the patient＇s clinical situation. Cryoglobulins were detected visibly by separation of cryoprecipitates in patient serum samples. Three IL-28B SNPs （rs8099917, rs12979860, and rs12980275） were detected by sequencing. Response to treatment was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline （prior to treatment initiation）, during treatment （4 and 12 weeks after treatment initiation）, end of therapy （48 weeks after treatment initiation）, and post-treatment （24 weeks after end of therapy）. The significance of between-group differences were assessed by the Chi-square and Fisher＇s exact tests. Results Cryoglobulinemia was detected in 43.5% （27/62） of the CHC patients and showed a female bias （59.3% vs. males： 34.3%, P = 0.05）. Compared toCHC patients without cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly higher levels of HCV RNA at baseline （5.64 ＋ 1.20 vs. 6.37± 0.67, P 〈 0.05） but lower frequencies of the IL28B rs8099917 TT genotype （94.3% vs. 63.0%, P = 0.002）, rs8099917 T allele （97.1% vs. 81.5%, P = 0.003）, and rs12979860 C allele （94.3% vs. 83.3%, P = 0.048）. CHC patients with cryoglobulinemia and having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a higher rate of sustained virological response. Conclusion Cryoglobulinemia in CHC patients is associated with a differential distribution of IL-28B polymoprhisms, and certain polymorphisms may be related to anti-viral treatment response.