Lack of Association Between MTHFR, MTR, MTRR, and TCN2 Genes and Nonsyndromic CL±P in a Chinese Population: Case-Control Study and Meta-Analysis
Lack of Association Between MTHFR, MTR, MTRR, and TCN2 Genes and Nonsyndromic CL±P in a Chinese Population: Case-Control Study and Meta-Analysis
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DOI：
10.1597/14.067
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发表时间：
2015-09-01
期刊：
影响因子：
--
通讯作者：
Song, Tao
中科院分区：
文献类型：
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作者：
Jiang, Chanyuan;Yin, Ningbei;Song, Tao
非综合征性唇裂伴或不伴腭裂（NSCLP）是一种常见的先天性畸形，常与叶酸缺乏有关。基因MTHFR、MTR、MTRR和TCN 2在叶酸代谢中起关键作用。与叶酸途径中的特定变体相关的NSCLP风险在种族群体之间存在差异。本研究的目的是探讨这四个基因的遗传变异以及基因-基因相互作用是否与NSCLP相关。我们调查了从中国人群HapMap数据中选择的MTHFR的7个tagSNPs、MTR的18个tagSNPs、MTRR的15个tagSNPs和TCN 2的7个tagSNPs。这些单核苷酸多态性（SNPs）与204例患者和226名对照的NSCLP进行了检查。然后，我们对rs 1801133和NSCLP之间的关联进行了荟萃分析。MTR中rs 4077829和rs 10802565的等位基因频率和单倍型分析在NSCLP组和对照组之间差异有统计学意义，但经10,000次排列校正后差异无统计学意义。其他SNPs的等位基因频率、单倍型分析和基因-基因相互作用没有显示出显著差异。Meta分析结果显示，等位基因比较、杂合子比较、纯合子比较、显性模型比较和隐性模型比较均无显著差异。与这些多态性相关的叶酸代谢改变不参与中国人群的NSCLP。
Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common congenital deformity, often associated with folate deficiency. The genes MTHFR, MTR, MTRR, and TCN2 play key roles in folate metabolism. The risk of NSCLP associated with particular variants in the folic acid pathway differs among ethnic groups. The goal of this study was to explore whether genetic variations in these four genes, as well as gene-gene interactions, are associated with NSCLP. We investigated 7 tagSNPs for MTHFR, 18 tagSNPs for MTR, 15 tagSNPs for MTRR, and 7 tagSNPs for TCN2 selected from HapMap data in a Chinese population. These single nucleotide polymorphisms (SNPs) were examined for associations with NSCLP in 204 patients and 226 controls. We then performed a meta-analysis of association between rs1801133 and NSCLP. There was a significant difference in the allele frequency and haplotype analysis of rs4077829 and rs10802565 in MTR between the NSCLP and control groups but not a significant difference after correction with 10,000 times permutations. The allele frequency, haplotype analysis, and gene-gene interactions of other SNPs did not show a significant difference. The meta-analysis results showed that no significant differences were found for allele comparison, heterozygote comparison, homozygote comparison, dominant model comparison, or recessive model comparison. The alterations of folate metabolism related to these polymorphisms are not involved in NSCLP in the Chinese population.