中国实用儿科杂志

中国实用儿科杂志 ›› 2012, Vol. 27 ›› Issue (3): 191-197.

• 论著 • 上一篇    下一篇

不同纬度下维生素D受体基因多态性
与佝偻病易感性关联性Meta分析

张鹏鹏1，陈莉莉1，李    颢2，王束玫1   

  1. 1.重庆医科大学附属儿童医院肾脏免疫科，重庆  400014；2.山东省立医院呼吸科（并列第一作者），济南    250021
  • 出版日期:2012-03-06 发布日期:2012-04-16

The association between vitamin D receptor gene polymorphisms and rickets susceptibility：a Meta-analysis. 

  • Online:2012-03-06 Published:2012-04-16

摘要：

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、Science Direct 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。

关键词: 维生素D受体, 佝偻病, Meta分析, 单核苷酸多态性

Abstract:

Objective    To assess the relationships between polymorphisms of ForkI，BsmI， ApaI，TaqI in vitamin D receptor gene and the susceptibility to rickets and to investigate whether their associations were dependent upon variants in latitude by Meta-analysis. Methods    A comprehensive search was conducted to identify all studies of the above-mentioned associations.Pooled ORs and their 95% CIs were calculated by either fixed or random effect pooled measure，which was selected on the basis of heterogeneity test among studies.Sub-group analysis was performed based on the different latitudes （high/low latitude）.Meta-regression was performed to assess the potentially important covariates exerting substantial impact on between-study heterogeneity. An analysis of influence was conducted， which described how robust the pooled estimator was to removal of each individual study . Publication bias was estimated using modified Egger’s linear regression test. Results    Compared with the controls，for overall and subgroup populations，the FokI polymorphism had a significantly protective effect on the risk of rickets in dominant，recessive and codominant models. For overall population the pooled ORs（95%CI） were 0.40（0.25～0.65），0.41（0.31～0.55） and 0.50（0.38～0.67） respectively. For high latitude area population the pooled ORs（95%CI） were 0.48（0.25～0.93），0.43（0.23～0.80） and 0.55（0.39～0.78） respectively. For low latitude area population the pooled ORs（95%CI） were 0.38（0.21～0.69），0.41（0.29～0.57） and 0.48（0.34～0.68） respectively. The BsmI polymorphism was found contributing significantly to rickets susceptibility for high latitude area population in dominant，recessive and codominant models and for overall population in dominant and codominant models.For high latitude area population the pooled ORs（95%CI）were 2.86（1.33～6.16），3.93（1.11～13.89）and 2.66（1.33～5.31）respectively.For overall population the pooled ORs（95%CI） were 2.15（1.11～4.16） and 1.85（1.09～3.16） respectively.The ApaI polymorphism was found to be a risk factor in the incidence of rickets only for overall population in recessive model.The TaqI polymorphism was found contributing significantly to rickets susceptibility only in recessive model for overall population and high latitude area population.Conclusion    This Meta-analysis suggests that the ForkI polymorphism was associated with a decreased risk of rickets，while the BsmI polymorphism is associated with an increased risk of rickets for only low sun-exposure population.The above-mentioned two associations appear to vary by the sun exposure levels.The ApaI and TaqI polymorphisms are not likely to be associated with rickets susceptibility.

Key words: vitamin D receptor, rickets, Meta-analysis, single nucleotide polymorphisms（SNPs）