PAX9 and TGFB3 are linked to susceptibility to nonsyndromic cleft lip with or without cleft palate in the Japanese:: population-based and family-based candidate gene analyses
PAX9 and TGFB3 are linked to susceptibility to nonsyndromic cleft lip with or without cleft palate in the Japanese:: population-based and family-based candidate gene analyses
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DOI：
10.1007/s10038-005-0319-8
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Yoshiura, K
中科院分区：
文献类型：
--
作者：
Ichikawa, E;Watanabe, A;Yoshiura, K
据信，日本人非综合征性唇腭裂（CL/P）和单纯腭裂（CPO）的患病率高于美国人、欧洲人和非洲人。本研究的目的是在日本人群中研究CL/P或CPO与7个候选基因（TGFB 3、DLX 3、PAX 9、CLPTM 1、TBX 10、PVRL 1、TBX 22）之间的关系，这些候选基因在其他人群中显示出正相关性，并在发育中小鼠的口腔/唇部区域表达。我们首先在112名CL/P和16名CPO患者中寻找这些基因的突变，并在来自日本家庭的两名CL/P同胞及其表型正常的母亲中发现PAX 9外显子3的杂合错义突变（640 A> G，S214 G）。一个基于人群的病例对照分析和一个基于家庭的传播不平衡检验（TDT），使用单核苷酸多态性（SNPs），和两个SNP单倍型的基因，112 CL/P的情况下，他们的父母和192个控制之间的显着关联，在一个SNP位点，IVS 1 + 5321，在TGFB 3的P值为0.0016。基于群体的单倍型分析显示，由IVS 1 + 5321和IVS 1 -1572组成的单倍型“A/A”的相关性最显著; TDT也给出了该单倍型的P值为0.0252。
The prevalence of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) are believed to be higher in the Japanese than in Americans, Europeans or Africans. The purpose of this study was to investigate, in a Japanese population, relationships between CL/P or CPO and seven candidate genes (TGFB3, DLX3, PAX9, CLPTM1, TBX10, PVRL1, TBX22) that showed positive associations in other populations and are expressed in the oral/lip region in developing mice. We first searched for mutations in these genes among 112 CL/P and 16 CPO patients, and found a heterozygous missense mutation (640A > G, S214G) in exon 3 of PAX9 in two sibs with CL/P and their phenotypically normal mother from a Japanese family. A population-based case-control analysis and a family-based transmission disequilibrium test (TDT), using single nucleotide polymorphisms (SNPs), and two-SNP haplotypes of the genes, between the 112 CL/P cases with their parents and 192 controls indicated a significant association at one SNP site, IVS1 + 5321, in TGFB3 with a P-value of 0.0016. Population-based haplotyping revealed that the association was most significant for haplotype "A/A" consisting of IVS1 + 5321 and IVS1-1572; TDT also gave a P-value of 0.0252 in this haplotype.