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Abstract：
This study aims to identify potential variants in the TP63-IRF6 pathway and GREM1 for the etiology of non-syndromic orofacial cleft (NSOFC) among the Vietnamese population. By collecting 527 case-parent trios and 527 control samples, we conducted a stratified analysis based on different NSOFC phenotypes, using allelic, dominant, recessive and over-dominant models for case-control analyses, and family-based association tests for case-parent trios. Haplotype and linkage disequilibrium analyses were also conducted. IRF6 rs2235375 showed a significant association with an increased risk for non-syndromic cleft lip and palate (NSCLP) and cleft lip with or without cleft palate (NSCL/P) in the G allele, with pallele values of 0.0018 and 0.0003, respectively. Due to the recessive model (p = 0.0011) for the NSCL/P group, the reduced frequency of the GG genotype of rs2235375 was associated with a protective effect against NSCL/P. Additionally, offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL/P compared to the C allele holders. IRF6 rs846810 and a G-G haplotype at rs2235375-rs846810 of IRF6 impacted NSCL/P, with p-values of 0.0015 and 0.0003, respectively. In conclusion, our study provided additional evidence for the association of IRF6 rs2235375 with NSCLP and NSCL/P. We also identified IRF6 rs846810 as a novel marker associated with NSCL/P, and haplotypes G-G and C-A at rs2235375-rs846810 of IRF6 associated with NSOFC.
摘要：
这项研究旨在确定TP63-IRF6途径和GREM1中的潜在变异，用于越南人群中非综合征性口面裂（NSOFC）的病因。通过收集527个案例-父母三重奏和527个对照样本，我们根据不同的NSOFC表型进行了分层分析，使用等位基因，支配,病例对照分析的隐性和过度显性模型，以及基于家庭的案例家长三重奏关联测试。还进行了单倍型和连锁不平衡分析。IRF6rs223375显示G等位基因与非综合征性唇腭裂（NSCLP）和唇裂伴或不伴腭裂（NSCL/P）的风险增加显著相关，pallelle值分别为0.0018和0.0003。由于NSCL/P组的隐性模型（p=0.0011），rs2235375的GG基因型频率降低与对NSCL/P的保护作用相关。此外,与C等位基因持有者相比，在rs225375遗传G等位基因的后代患NSCL/P的风险增加了1.34倍。IRF6rs846810和在IRF6的rs225375-rs846810处的G-G单倍型受影响的NSCL/P，p值分别为0.0015和0.0003。总之,我们的研究为IRF6rs2235375与NSCLP和NSCL/P的关联提供了额外的证据。我们还将IRF6rs846810鉴定为与NSCL/P相关的新标记，以及与NSOFC相关的IRF6的rs2233375-rs846810处的单倍型G-G和C-A。
