Lack of Association between Missense Variants in GRHL3 (rs2486668 and rs545809) and Susceptibility to Non-Syndromic Orofacial Clefts in a Han Chinese Population.
Lack of Association between Missense Variants in GRHL3 (rs2486668 and rs545809) and Susceptibility to Non-Syndromic Orofacial Clefts in a Han Chinese Population.
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GRHL3 错义变异（rs2486668 和 rs545809）与中国汉族人群非综合征性口面部裂易感性之间缺乏关联
DOI：
10.1371/journal.pone.0159940
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Bian Z
中科院分区：
文献类型：
--
作者：
He M;Bian Z
研究背景Grainyhead-like-3（GRHL 3）是近年来发现的第二个可导致以口面裂（orofacial clefts，OFC）和下唇凹陷为特征的货车德沃德综合征（Van der Woude syndrome）的基因。此外，GRHL 3的错义变异（rs 41268753）赋予欧洲血统的非综合征性腭裂病例的风险。GRHL 3与干扰素调节因子6（IRF 6）可能与非固体氧化物燃料电池的风险有关，有待在不同种族人群中验证。目的探讨中国汉族人群中GRHL 3基因常见功能变异与非手术性口腔颌面畸形（NSOFC）易感性的关系，尤其是腭裂患者。方法由于中国汉族人群中rs 41268753次要等位基因频率为零，我们选择了中国汉族人群中次要等位基因频率（MAF）> 5%的功能性单核苷酸多态性（SNP）。然后使用TaqMan 5′-外切核酸酶等位基因鉴别试验在包括1145个个体的病例对照队列中对符合上述标准的两个SNP进行基因分型。结果本研究使用的SNPs为rs 2486668和rs 545809。两种SNPs的总体基因型和等位基因分布在一般和分层基因分型分析中显示病例组和对照组之间无统计学显著差异。使用不同遗传模型的进一步逻辑回归分析未能揭示这些标记物影响NSOFC风险的任何证据。结论GRHL 3基因rs 41268753变异增加了欧洲人群腭裂的风险，但我们的研究结果未能检测到两个GRHL 3单核苷酸多态性（rs 2486668和rs 545809）与中国汉族人群NSOFC风险之间的联系。虽然本研究没有提供任何证据表明GRHL 3的常见功能变异可能导致中国人群中的NSOFC病因，但仍需要进一步研究更大的样本量，额外的SNP和更多样化的种族队列。
Background Grainyhead-like-3 (GRHL3) was recently identified as the second gene that, when mutated, can leads to Van der Woude syndrome, which is characterized by orofacial clefts (OFC) and lower lip pits. In addition, a missense variant (rs41268753) in GRHL3 confers risk for non-syndromic cleft palate cases of European ancestry. Together with interferon regulatory factor 6 (IRF6), GRHL3 may be associated with the risk of NSOFC which awaits for being verified across different ethnic populations. Objective The aim of this study was to investigate the possible relationship between common functional variants in GRHL3 and susceptibility to NSOFC, especially cleft palate cases, in a Han Chinese population, one of the ethnic groups with the highest birth prevalence of orofacial clefting. Methods Because the allele frequency for rs41268753 minor alleles was zero in our Chinese population, we selected functional single nucleotide polymorphisms (SNPs) spanning GRHL3 with minor allele frequencies (MAFs) > 5% in the Han Chinese population. Two SNPs which meet the above criteria were then genotyped in a case-control cohort comprising 1145 individuals using the TaqMan 5′-exonuclease allelic discrimination assay. Results SNPs rs2486668 and rs545809 were used in this study. Overall genotype and allele distributions of both SNPs in general and stratified genotyping analyses revealed no statistically significant differences between cases and controls. Further logistic regression analyses using different genetic models failed to reveal any evidence that these markers influence risk to NSOFC. Conclusions The variant rs41268753 in GRHL3 increases the risk for cleft palate in European population, but our findings failed to detect the link between two GRHL3 SNPs (rs2486668 and rs545809) and risk to NSOFC in the Han Chinese cohort. Although the present study did not provide any evidence that common functional variants in GRHL3 may contribute to NSOFC etiology in this Chinese population, further studies with a larger sample size, additional SNPs, and a more diverse ethnic cohort are still warranted.