Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan, China.
PLoS One. 2011;6(9):e25603. doi: 10.1371/journal.pone.0025603. Epub 2011 Sep 29.
HOXA1 and HOXB1 have been strongly posed as candidate genes for autism spectrum disorders (ASD) given their important role in the development of hindbrain. The A218G (rs10951154) in HOXA1 and the insertion variant in HOXB1 (nINS/INS, rs72338773) were of special interest for ASD but with inconclusive results. Thus, we conducted a meta-analysis integrating case-control and transmission/disequilibrium test (TDT) studies to clearly discern the effect of these two variants in ASD.
Multiple electronic databases were searched to identify studies assessing the A218G and/or nINS/INS variant in ASD. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. A total of 10 and 7 reports were found to be eligible for meta-analyses of A218G and nINS/INS variant, respectively. In overall meta-analysis, the pooled OR for the 218G allele and the INS allele was 0.97 (95% CI = 0.76-1.25, P(heterogeneity) = 0.029) and 1.14 (95% CI = 0.97-1.33, P(heterogeneity) = 0.269), respectively. No significant association was also identified between these two variants and ASD risk in stratified analysis. Further, cumulative meta-analysis in chronologic order showed the inclination toward null-significant association for both variants with continual adding studies. Additionally, although the between-study heterogeneity regarding the A218G is not explained by study design, ethnicity, and sample size, the sensitive analysis indicated the stability of the result.
This meta-analysis suggests the HOXA1 A218G and HOXB1 nINS/INS variants may not contribute significantly to ASD risk.
HOXA1 和 HOXB1 在后脑发育中起着重要作用，因此被强烈认为是自闭症谱系障碍 (ASD) 的候选基因。HOXA1 中的 A218G(rs10951154) 和 HOXB1 中的插入变体(nINS/INS，rs72338773) 特别引起了人们对 ASD 的关注，但结果尚无定论。因此，我们进行了一项荟萃分析，整合病例对照和传递/不平衡测试 (TDT) 研究，以清楚地区分这两种变体在 ASD 中的作用。
通过多个电子数据库搜索评估 ASD 中 A218G 和/或 nINS/INS 变体的研究。使用 Catmap 软件，以等位基因模型分析病例对照和 TDT 研究的数据。总共发现 10 项和 7 项报告分别适合对 A218G 和 nINS/INS 变体进行荟萃分析。在总体荟萃分析中，218G 等位基因和 INS 等位基因的汇总 OR 分别为 0.97(95%CI=0.76-1.25，P(异质性)=0.029)和 1.14(95%CI=0.97-1.33，P(异质性)=0.269)。在分层分析中，也没有发现这两种变体与 ASD 风险之间存在显著关联。此外，按时间顺序进行的累积荟萃分析表明，随着研究的不断增加，这两种变体与关联的倾向趋于无显著意义。此外，尽管 A218G 的研究间异质性不能用研究设计、种族和样本大小来解释，但敏感性分析表明结果是稳定的。
这项荟萃分析表明，HOXA1 A218G 和 HOXB1 nINS/INS 变体可能不会显著增加 ASD 的风险。
