State Key Laboratory of Oral Disease and Department of Cleft Lip and Palate Surgery, West China College of Stomatology, Sichuan University, Chengdu, PR China.
DNA Cell Biol. 2011 Jan;30(1):47-54. doi: 10.1089/dna.2010.1082. Epub 2010 Sep 17.
The etiology of nonsyndromic orofacial clefts (NSOC) has been considered "complex" or "multifactorial." Etiologic heterogeneity induces disparities in the results among different populations. The zinc finger protein 533 (ZNF533) and several environmental factors have been revealed to be associated with NSOC in several populations. We investigated three single-nucleotide polymorphisms (SNPs) and 10 environmental factors in 211 case-parent trios and 188 control individuals in the Western Han Chinese population to confirm the relationship between ZNF533, environmental factors, and the etiology of NSOC in the Western Han Chinese population. The transmission disequilibrium test, case-control analysis, multiple logistic regression, log-linear model, and conditional logistic regression were tested to confirm the contribution of the ZNF533 gene and environmental factors to the etiology of NSOC. Strong statistically significant evidence of association was found between the rs6757845 and rs1139 markers and NSOC. The haplotype G-G for rs6757845-rs1139 showed significant overtransmission among cleft lip with or without cleft palate (CL/P) trios and among cleft palate only trios. Additional 11 and 5 haplotypes were significantly overtransmitted and undertransmitted among CL/P and among cleft palate only trios, respectively. Maternal disease, use of medication, and passive smoking during the first trimester of pregnancy may increase the risk of NSOC. Maternal folic acid supplementation during the first trimester of pregnancy showed a protective effect on the etiology of NSOC. Genotype-environment interaction test showed a significant evidence of interaction effects between the genotypes at rs6757845 and maternal passive smoking during the first trimester among CL/P trios. These results confirm the effects of the ZNF533 gene and environmental factors on the etiology of NSOC.
非综合征性口腔颌面裂（NSOC）的病因被认为是“复杂的”或“多因素的”。病因异质性导致不同人群之间的结果存在差异。锌指蛋白 533（ZNF533）和几个环境因素已被揭示与多个人群中的 NSOC 相关。我们在西方汉族人群中调查了 211 个病例-父母三体型和 188 个对照个体中的三个单核苷酸多态性（SNP）和 10 个环境因素，以确认 ZNF533、环境因素与西方汉族人群 NSOC 病因之间的关系。进行了传递不平衡检验、病例对照分析、多因素逻辑回归、对数线性模型和条件逻辑回归，以确认 ZNF533 基因和环境因素对 NSOC 病因的贡献。rs6757845 和 rs1139 标记物与 NSOC 之间存在强烈的统计学显著关联证据。rs6757845-rs1139 的 G-G 单体型在唇裂伴或不伴腭裂（CL/P）三体型和单纯腭裂三体型中表现出明显的过度传递。在 CL/P 和单纯腭裂三体型中，分别有 11 个和 5 个单体型明显过度传递和不足传递。妊娠早期母亲患病、用药和被动吸烟可能会增加 NSOC 的风险。妊娠早期母亲补充叶酸对 NSOC 的病因具有保护作用。基因型-环境相互作用检验显示，rs6757845 基因型与妊娠早期母亲被动吸烟之间在 CL/P 三体型中存在显著的相互作用效应证据。这些结果证实了 ZNF533 基因和环境因素对 NSOC 病因的影响。
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