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目的探讨4个常见维生素D受体(VDR)基因位点(ForkI、BsmI、ApaI、TaqI)单核苷酸多态性(SNPs)与佝偻病易感性关联性并探讨日照量对其的影响。方法制定原始文献的纳入和排除标准及检索策略。检索1980年1月至2011年1月中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)、数字化期刊全文数据库(万方)、中国生物医学文献数据库(CBM)及PubMed、CALIS、ScienceDirect数据库中4个位点SNPs与佝偻病易感性关联性关系为研究内容的文献,提取数据。对研究间异质性进行检验并选用适当模型对总人群及高、低纬度两个亚组人群分别进行数据合并,得出合并比值比(OR)及95%置信区间(CI)。探讨研究间异质性来源,最后进行影响性分析及发表偏倚检验。结果共纳入22篇文献。Meta分析结果显示,ForkI位点总人群及亚组人群显性、隐性、共显性遗传模型分析均提示病例f等位基因暴露比低于对照组,差异具有统计学意义。总人群3个遗传模型合并OR(95%CI)分别为0.40(0.25～0.65)、0.41(0.31～0.55)、0.50(0.38～0.67);高纬度人群分别为0.48(0.25～0.93)、0.43(0.23～0.80)、0.55(0.39～0.78);低纬度人群分别为0.38(0.21～0.69)、0.41(0.29～0.57)、0.48(0.34～0.68)。BsmI位点总人群显性、共显性模型及高纬度人群3个遗传模型分析均提示病例B等位基因暴露比高于对照组,差异有统计学意义(P<0.05)。总人群显性、共显性模型合并OR(95%CI)分别为2.15(1.11～4.16)、1.85(1.09～3.16);高纬度人群3个遗传模型合并OR(95%CI)分别为2.86(1.33～6.16)、3.93(1.11～13.89)、2.66(1.33～5.31);低纬度人群差异无统计学意义。ApaI位点仅在总人群隐性模型分析中发现其多态性与佝偻病易感性关联有统计学意义。TaqI位点仅在总人群及高纬度人群隐性模型分析中发现其多态性与佝偻病易感性关联有统计学意义。影响性分析显示Meta分析结果稳定,可信度较高。结论 ForkI位点f等位基因可降低佝偻病易感性;BsmI位点B等位基因使日照贫乏地区人群更易患佝偻病;ApaI、TaqI位点SNPs可能与佝偻病易感性无关。ForkI、BsmI位点与佝偻病易感性关联可能受研究对象日照暴露量影响。
Objective To investigate the association between single nucleotide polymorphisms (SNPs) of four common vitamin D receptor (VDR) gene loci (ForkI, BsmI, ApaI, TaqI) and susceptibility to rickets and explore the effect of sunshine. Methodology Development of inclusion and exclusion criteria and search strategies for original documents. To search the Chinese Journal Full-text Database (CNKI), Chinese Science and Technology Periodical Database (VIP), Digital Periodical Full-text Database (Wanfang), China Biomedical Literature Database (CBM) and PubMed, CALIS and ScienceDirect database from January 1980 to January 2011, In the four SNPs and the relationship between susceptibility to rickets as the content of the literature, data extraction. The heterogeneity of the study was tested and the appropriate models were selected for the combined data of the total population and the high and low latitudes of two subgroups to obtain the combined odds ratio (OR) and 95% confidence interval (CI). Explore sources of heterogeneity among studies, and finally conduct impact analysis and publication bias tests. Results A total of 22 articles were included. The results of Meta analysis showed that the dominant and recessive co-dominant genetic model analysis of total Fork I locus and subpopulation population suggested that the allele frequency of f allele was lower than that of the control group, and the difference was statistically significant. The OR of 95% CI for the three population-based genetic models were 0.40 (0.25-0.65), 0.41 (0.31-0.55) and 0.50 (0.38-0.67), respectively. The high latitude population was 0.48 (0.25-0.93) and 0.43 0.23-0.80) and 0.55 (0.39-0.78) respectively. The population at low latitude was 0.38 (0.21-0.69), 0.41 (0.29-0.57) and 0.48 (0.34-0.68), respectively. The analysis of 3 genetic models in dominant and co-dominant population and high-latitude population in the total population of BsmI sites indicated that the B allele exposure ratio was higher than that of the control group (P <0.05). The odds ratio (95% CI) of the dominant and co-dominant models were 2.15 (1.11-4.16) and 1.85 (1.09-3.16), respectively. The OR of 95% CI for the three high-latitude population genetic models were 2.86 1.33 ~ 6.16), 3.93 (1.11 ~ 13.89), 2.66 (1.33 ~ 5.31). There was no significant difference in low latitude population. ApaI locus was found only in the general population implicit model analysis found that the polymorphism associated with rickets susceptibility was statistically significant. The TaqI locus showed only a significant association with the susceptibility to rickets in the total population and high-latitude recessive model analysis. Impact analysis showed that the Meta analysis was stable with high confidence. Conclusions F allele at ForkI locus can reduce the susceptibility to rickets. B allele at BsmI locus makes rickets more susceptible to rodents in poor sunshine areas. SNPs at ApaI and TaqI sites may not be related to susceptibility to rickets. The association of ForkI, BsmI sites with susceptibility to rickets may be affected by exposure to sunlight.