中国人群中干扰素调节因子6基因多态性与非综合征性唇裂伴或不伴腭裂的关联

Association between interferon regulatory factor 6 gene polymorphisms and nonsyndromic cleft lip with or without cleft palate in a chinese population.

作者信息

Zhou Qian, Li Mengjie, Zhu Wenli, Guo Jinzhen, Wang Yun, Li Yong, Li Shuqin

出版信息

Cleft Palate Craniofac J. 2013 Sep;50(5):570-6. doi: 10.1597/12-234. Epub 2013 Mar 19.

Abstract

Objective : To further confirm the association between two IRF6 single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate in a Chinese population. Participants : A total of 106 nonsyndromic cleft lip with or without cleft palate case trios and 129 control trios. Intervention : Two IRF6 single nucleotide polymorphisms, rs2235371 and rs642961, were genotyped for all case and control families. Case-control analysis and family-based linkage analysis were both performed for the two single nucleotide polymorphisms. Results : The genotype and allele frequencies of rs2235371 (odds ratioAG+AA vs. GG, 0.581; 95% confidence interval, 0.345 to 0.976; P = .039) and rs642961 (odds ratioAG+AA vs. GG, 5.389; 95% confidence interval, 2.936 to 9.893; P = 5e-08) were significantly higher in nonsyndromic cleft lip with or without cleft palate patients compared with controls. There was an obvious dosage effect of allele A at rs642961. The transmission of a major allele (G) of rs2235371 and a minor allele (A) of rs642961 was in disequilibrium (P < .05) in complete case-parent trios. The association between the two single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate was confirmed by the Family-Based Association Test for rs642961 (P = .008), but there was no significance for rs2235371 (P = 0.057). Haplotype analysis found that rs2235371 G/rs642961 A haplotype increased the risk of nonsyndromic cleft lip with or without cleft palate (P = 2.42e-07); whereas, rs2235371 A/rs642961 G haplotype reduced the risk of nonsyndromic cleft lip with or without cleft palate (P = 4.37e-05). No evidence of linkage disequilibrium was found between the two single nucleotide polymorphisms (D' = 0.303, r(2) = 0.017). Conclusion : Our results confirmed the involvement of the IRF6 variants rs642961 and rs2235371 in the etiology of nonsyndromic cleft lip with or without cleft palate in a Chinese population.

摘要

目的

进一步在中国人群中证实两个IRF6单核苷酸多态性与非综合征性唇腭裂（伴或不伴腭裂）之间的关联。

参与者

总共106个非综合征性唇腭裂（伴或不伴腭裂）病例三联体和129个对照三联体。

干预措施

对所有病例和对照家庭的两个IRF6单核苷酸多态性rs2235371和rs642961进行基因分型。对这两个单核苷酸多态性进行病例对照分析和基于家系的连锁分析。

结果

rs2235371（AG + AA与GG的比值比，0.581；95%置信区间，0.345至0.976；P = 0.039）和rs642961（AG + AA与GG的比值比，5.389；95%置信区间，2.936至9.893；P = 5×10⁻⁸）的基因型和等位基因频率在非综合征性唇腭裂（伴或不伴腭裂）患者中显著高于对照组。rs642961处的等位基因A存在明显的剂量效应。在完整的病例 - 父母三联体中，rs2235371的一个主要等位基因（G）和rs642961的一个次要等位基因（A）的传递处于不平衡状态（P < 0.05）。基于家系的关联检验证实rs642961的两个单核苷酸多态性与非综合征性唇腭裂（伴或不伴腭裂）之间存在关联（P = 0.008），但rs2235371无显著性（P = 0.057）。单倍型分析发现rs2235371 G/rs642961 A单倍型增加了非综合征性唇腭裂（伴或不伴腭裂）的风险（P = 2.42×10⁻⁷）；而rs2235371 A/rs642961 G单倍型降低了非综合征性唇腭裂（伴或不伴腭裂）的风险（P = 4.37×e⁻⁵）。未发现两个单核苷酸多态性之间存在连锁不平衡的证据（D' = 0.303，r² = .017）。