SNPs and interaction analyses of IRF6, MSX1 and PAX9 genes in patients with non‑syndromic cleft lip with or without palate.
Non‑syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital deformity, often associated with missing or deformed teeth. The genes interferon regulatory factor 6 (IRF6), muscle segment homeobox 1 (MSX1) and paired box gene 9 (PAX9) are important for the development of the maxillofacial region and dentition. The aim of this study was to explore how genetic variations in IRF6, MSX1 and PAX9, as well as gene‑gene interactions, are associated with NSCL/P. We investigated 9 IRF6 tag single nucleotide polymorphisms (SNPs), 2 MSX1 tag SNPs and 8 PAX9 tag SNPs selected from HapMap data from the Chinese population. The SNPs were examined for associations with NSCL/P in 204 patients and 226 controls. The results demonstrated a significant association between NSCL/P and rs2073485, rs2235371, rs2236909 and rs861020 in the IRF6 gene, and haplotype analysis supported these findings. A marginally significant difference was observed in the NSCL/P group for rs17176643 in the PAX9 gene compared to the control group. The results of gene‑gene interaction analyses also indicated that the combination of rs2073485, rs2235371 or rs2236909 in IRF6 and rs17176643 in PAX9, increased the risk of NSCL/P. Thus, our study provided additional understanding of IRF6 variations in patients with NSCL/P and suggested that interactions between the IRF6 and PAX9 genes are potentially important for susceptibility to NSCL/P.
Center of Cleft Lip and Palate, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shijingshan, Beijing 100144, P.R. China.
Tao
T
Song
Di
D
Wu
Yongqian
Y
Wang
Haidong
H
Li
Ningbei
N
Yin
Zhenmin
Z
Zhao
D016022:Case-Control Studies; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium; D051957:MSX1 Transcription Factor / Q000235:genetics*; D008297:Male; D051764:PAX9 Transcription Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human