State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of cleft lip and palate, West China Hospital of Stomatology, Sichuan University, China.
Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, California, USA.
Oral Dis. 2023 Apr;29(3):1115-1127. doi: 10.1111/odi.14100. Epub 2021 Dec 27.
Considering limitations of previous studies and differences across populations and subtypes, this study aimed to identify new potential SNPs around IRF6 associated with non-syndromic orofacial cleft (NSOC) in Western Han Chinese.
We recruited 376 NSOC case-parent trios, including 125 non-syndromic cleft lip only (NSCLO) trios, 151 non-syndromic cleft lip and palate (NSCLP) trios, and 100 non-syndromic cleft palate only (NSCPO) trios. Twenty-two single-nucleotide polymorphisms (SNPs) were genotyped using MassARRAY method. Hardy-Weinberg equilibrium test, allelic transmission disequilibrium test (TDT) analysis, sliding-window haplotype TDT analysis, and tests for parent-of-origin effect were performed using the PLINK software. Pairwise linkage disequilibrium (LD) was computed using the Haploview program.
In TDT analysis, allele A at rs17015217 (p = 0.00011, OR = 0.61 and 95% CI: 0.47-0.78) and allele T at rs12080691 (p = 0.00011, OR = 0.61 and 95% CI: 0.47-0.78) were under-transmitted among NSCLO trios but over-transmitted among NSCPO trios. Haplotypes showing evidence of under-transmission in NSCLO trios were over-transmitted in NSCPO trios. In tests for parent-of-origin effects, T allele at rs12080691 presented paternal under-transmission among NSCLO trios but over-transmission among NSCPO trios.
Allele A at rs17015217 and allele T at rs12080691 are associated with NSCLO and NSCPO with potential to have opposite effects on two subtypes in this sample from Western Han Chinese.
考虑到以往研究的局限性以及不同人群和亚型之间的差异，本研究旨在鉴定与西方汉族人群中非综合征性口面裂（NSOC）相关的 IRF6 周围新的潜在单核苷酸多态性（SNP）。
我们招募了 376 个 NSOC 病例-父母三体型，包括 125 个非综合征性单纯唇裂（NSCLO）三体型、151 个非综合征性唇腭裂（NSCLP）三体型和 100 个非综合征性单纯腭裂（NSCPO）三体型。采用 MassARRAY 方法对 22 个单核苷酸多态性（SNP）进行基因分型。使用 PLINK 软件进行 Hardy-Weinberg 平衡检验、等位基因传递不平衡检验（TDT）分析、滑动窗口单体型 TDT 分析和双亲来源效应检验。使用 Haploview 程序计算成对连锁不平衡（LD）。
在 TDT 分析中，rs17015217 处的等位基因 A（p=0.00011，OR=0.61，95%CI：0.47-0.78）和 rs12080691 处的等位基因 T（p=0.00011，OR=0.61，95%CI：0.47-0.78）在 NSCLO 三体型中呈未传递状态，但在 NSCPO 三体型中呈传递过度状态。在 NSCLO 三体型中显示未传递的单体型在 NSCPO 三体型中呈传递过度状态。在双亲来源效应检验中，rs12080691 处的 T 等位基因在 NSCLO 三体型中呈父源未传递状态，但在 NSCPO 三体型中呈传递过度状态。
rs17015217 处的等位基因 A 和 rs12080691 处的等位基因 T 与 NSCLO 和 NSCPO 相关，在本来自西方汉族的样本中，这两个等位基因对两个亚型可能具有相反的作用。
