Wang X-M, Wu Y-W, Li Z-J, Zhao X-H, Lv S-M, Wang X-H
Department of Nephrology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
Second Department of Gastroenterology, Shaanxi Provincial People's Hospital, No. 256 West Youyi Road, Xi'an, 710068, Shaanxi, China.
J Endocrinol Invest. 2016 Jun;39(6):617-25. doi: 10.1007/s40618-015-0405-5. Epub 2015 Dec 28.
To evaluate correlations between polymorphisms of calcium-sensing receptor (CASR) gene [A986S (rs1081725), R990G (rs1042636) and Q1011E (rs1801726)] and the risk of primary hyperparathyroidism (PHPT) among human population.
Relevant studies were retrieved from online databases using computer-based search strategies, which were then supplemented by manual search strategies. Case-control studies related to our topic were identified based on strict inclusion and exclusion criteria. Statistical analyses were conducted using the Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA).
We retrieved 202 studies from online databases and other sources initially and eventually enrolled six studies into our meta-analysis. These six studies contained a sum of 693 PHPT patients and 1252 healthy controls. Our meta-analysis results showed that single nucleotide polymorphisms (SNPs) of CASR gene A986S (rs1081725) and R990G (rs1042636), but not Q1011E (rs1801726), may increase the risk of PHPT [A986S (rs1081725): allele model: P = 0.013; dominant model: P = 0.044; R990G (rs1042636): allele model: P = 0.023; dominant model: P = 0.026)]. Subgroup analyses based on ethnicity showed that among Asians, A986S (rs1081725) increased the PHPT risk (P = 0.04) under the allele model, but not under the dominant model. Among Caucasians, there was no association between gene frequencies and PHPT under both the allele and dominant model. In Asians, no significant association was observed between R990G (rs1042636) and PHPT risk, but in Caucasians, R990G (rs1042636) significantly increased the incidence of PHPT [R990G (rs1042636): allele model: P = 0.015; dominant model: P = 0.009)].
Our results indicate that SNPs of CASR gene A986S (rs1081725) and R990G (rs1042636) may increase the risk of PHPT, and the polymorphisms can potentially be used as important biological markers for early diagnosis of PHPT.
评估钙敏感受体（CASR）基因多态性[A986S（rs1081725）、R990G（rs1042636）和Q1011E（rs1801726）]与人群原发性甲状旁腺功能亢进症（PHPT）风险之间的相关性。
使用基于计算机的检索策略从在线数据库中检索相关研究，然后辅以手动检索策略。根据严格的纳入和排除标准确定与我们主题相关的病例对照研究。使用综合荟萃分析2.0（美国新泽西州恩格尔伍德的Biostat公司）进行统计分析。
我们最初从在线数据库和其他来源检索到202项研究，最终纳入6项研究进行荟萃分析。这6项研究共包含693例PHPT患者和1252例健康对照。我们的荟萃分析结果显示，CASR基因的单核苷酸多态性（SNP）A986S（rs1081725）和R990G（rs1042636）而非Q1011E（rs1801726）可能会增加PHPT的风险[A986S（rs1081725）：等位基因模型：P = 0.013；显性模型：P = 0.044；R990G（rs1042636）：等位基因模型：P = 0.023；显性模型：P = 0.026]。基于种族的亚组分析显示，在亚洲人中，等位基因模型下A986S（rs1081725）增加了PHPT风险（P = 0.04），但显性模型下未增加。在白种人中，等位基因模型和显性模型下基因频率与PHPT之间均无关联。在亚洲人中，未观察到R990G（rs1042636）与PHPT风险之间存在显著关联，但在白种人中，R990G（rs1042636）显著增加了PHPT的发病率[R990G（rs1042636）：等位基因模型：P = 0.015；显性模型：P = 0.009]。
我们的结果表明，CASR基因的SNP A986S（rs108172_）和R990G（rs1042）可能会增加PHPT的风险，并且这些多态性有可能作为PHPT早期诊断的重要生物学标志物。
