IL-6-174G>C和-634C>G多态性与2型糖尿病肾病关联荟萃分析

Associations of IL-6-174G>C and-634C>G polymorphisms with type 2 diabetic nephropathy:a meta-analysis

目的用荟萃(meta)分析IL-6-174G>C(rs1800795)和IL-6-634C>G(rs1800796,即572C/G)多态性与2型糖尿病肾病(DN)的关系。方法全面检索Pubmed、Embace和中国知网、万方、维普等数据库,收集建库至2017年4月关于IL-6-174G>C和-634C>G多态性与2型DN关联的研究。用STATA 14.0和Review manager 5.3软件进行统计分析:符合条件研究的异质性通过Q检验和I2检验进行评估,当发现重大异质性时,使用随机效应模型进行meta分析,否则使用固定效应模型;漏斗图和Begger图检测纳入文献是否发生偏倚;计算合并的优势比(OR)和相应的95%置信区间(95%CI),以评估IL-6-174G>C和-634C>G多态性与2型DN的关联,并根据不同地域人群进行亚组分析。结果共纳入11篇文献,IL-6-174G>C和-634C>G多态性与2型DN关联性研究分别纳入研究对象1 688及2 180例。亚洲人群IL-6-174G>C多态性与2型DN关联性分析中,等位基因遗传模型(OR=0.461,95%CI:0.274~0.777,P<0.01)、纯合子模型(OR=0.126,95%CI:0.022~0.734,P=0.021)、隐性遗传模型(OR=0.146,95%CI:0.026~0.827,P=0.030)、显性遗传模型(OR=0.504,95%CI:0.273~0.930,P=0.028)均有统计学意义,而杂合子模型(OR=0.606,95%CI:0.321~1.143,P=0.122)无统计学意义;欧洲人群IL-6-174G>C多态性与2型DN关联性分析无统计学意义。亚洲人群IL-6-634C>G多态性与2型DN关联性分析中,等位基因遗传模型(OR=1.467,95%CI:1.238~1.737,P<0.01)、纯合子模型(OR=2.793,95%CI:1.844~4.230,P<0.01)、隐性遗传模型(OR=2.296,95%CI:1.586~3.323,P<0.01)、显性遗传模型(OR=1.377,95%CI:1.109~1.711,P<0.01)均有统计学意义,而杂合子模型(OR=1.733,95%CI:0.932~1.476,P=0.174)无统计学意义;欧洲人群IL-6-634C>G多态性与2型DN关联性分析无统计学意义。结论亚洲人群IL-6-174 CC基因型对2型DN具有保护作用,IL-6-634 GG基因型可促进2型DN的发展。而欧洲人群IL-6-174G>C和-634C>G多态性与2型DN没有关联。

Objective To perform a meta-analysis on the associations of interleukin （IL）-6-174G 〉 C （rs1800795） and-634C 〉 G （rs1800796） polymorphisms with type 2 diabetic nephropathy （DN）. Methods The data on the studies about the associations of IL-6-174G 〉 C and-634C 〉 G polymoqphisms with type 2 DN were collected from Pubmed, Embaee, CNKI, Wan Fang and VIP data- base during their inception and April 2017. The statistical analysis was performed with STATA 14.0 and Review manager 5.3 soft- wares. The heterogeneity in the eligible studies was assessed by Q-statistic and 12 statistic. When the significant heterogeneity was found, the random effect model was used for meta-analysis, otherwise, the fixed effect model was used. The publication bias was evalu- ated with funnel and Begger graphs. The pooled odds ratios （OR） and corresponding 95% confidence intervals （95% CI） were calcu- lated for evaluating the associations of IL-6-174G 〉 C and-634C 〉 G polymorphisms with type 2 DN. In addition, the sub-group analysis was performed according to the regions of subjects. Results A total of 11 studies were enrolled, The studies on the association of IL-6-174G 〉 C polymorphism with type 2 DN included 1 688 subjects, while those on the association of IL-6-634C 〉 G with type 2 DN included 2 180 subjects. In the association analysis of IL-6-174G 〉 C polymorphism with type 2 DN of Asian population, the significant relationship was detected in an allelic genetic model （OR =0. 461, 95% CI： 0. 274-0. 777, P 〈0.01 ）, a homozygote model （OR = 0. 126, 95% CI： 0. 022-0. 734, P = 0. 021 ）, a recessive genetic model （ OR = 0. 146, 95% CI： 0. 026-0. 827, P = 0. 030） and a dominant genetic model （OR =0. 504, 95% CI： O. 273-0. 930, P =0. 028 ） , but not in a heterozygote model （OR = 0. 606, 95% CI： 0.321-1. 143, P =0. 122）. There was no significant relationship between IL-6-174G 〉 C polymorphism and type 2 DN in European population. In the association analysis of IL-6-634C 〉 G polymorphism with type 2 DN of Asian population, the significant relationship was found in an allelic genetic model （ OR = 1. 467, 95 % CI： 1. 238-1. 737, P 〈 0.01 ）, a homozygote model （ OR = 2. 793, 95 % CI： 1. 844-4.230, P = O. 021 ）, a recessive genetic model （ OR = 2. 296, 95 % CI： 1. 586-3. 323, P 〈 0.01 ） and a dominant genetic model （OR = 1.377, 95%CI： 1. 109-1. 711, P 〈 0.01）, but not in a heterozygote model （OR = 1. 733, 95% CI： O. 932-1. 476, P = 0. 174）. There was no significant relationship between IL-6-634C 〉 G polymorphism and type 2 DN in European population. Conclusion In Asian population, IL-6-174CC genotype may prevent the progression of type 2 DN, however, IL-6-.634GG genotype may promote the development of type 2 DN. But in European population, there is no relationship between IL-6-174G 〉 C and-634C 〉 G poly- morphisms and type 2 DN.