TGFA and IRF6 contribute to the risk of nonsyndromic cleft lip with or without cleft palate in northeast China.
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) are common birth defects with a complex etiology. Multiple interacting loci and possible environmental factors influence the risk of NSCL/P. 12 single nucleotide polymorphisms (SNPs) in 7 candidate genes were tested using an allele-specific primer extension for case-control and case-parent analyses in northeast China in 236 unrelated patients, 185 mothers and 154 fathers, including 128 complete trios, and 400 control individuals. TGFA and IRF6 genes showed a significant association with NSCL/P. In IRF6, statistical evidence of an association between rs2235371 (p = 0.003), rs2013162 (p<0.0001) and NSCL/P was observed in case-control analyses. Family based association tests (FBATs) showed over-transmission of the C allele at the rs2235371 polymorphism (p = 0.007). In TGFA, associations between rs3771494, rs3771523 (G3822A), rs11466285 (T3851C) and NSCL/P were observed in case-control and FBAT analyses. Associations between other genes (BCL3, TGFB3, MTHFR, PVRL1 and SUMO1) and NSCL/P were not detected.
Key Laboratory of Reproductive Health, Liaoning Province Research Institute of Family Planning, Shenyang, China.
Yongping
Y
Lu
Qiang
Q
Liu
Wei
W
Xu
Zengjian
Z
Li
Miao
M
Jiang
Xuefu
X
Li
Ning
N
Zhao
Wei
W
Liu
Yu
Y
Sui
Chao
C
Ma
Wenhua
W
Feng
Weitian
W
Han
Jianxin
J
Li
D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002681:China / Q000453:epidemiology; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics*
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D016211:Transforming Growth Factor alpha