[Association study between candidate genes involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate in Chinese population].
OBJECTIVE
To explore the association and gene-environment interaction between single nucleotide polymorphisms (SNPs) involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Chinese population.


METHODS
A total of 806 NSCL/P trios were drawn by an international consortium, which conducted a genome-wide association study (GWAS) using a case-parent trio design to investigate genes affecting risks to NSCL/P. The transmission disequilibrium test (TDT) was used to explore the association between cell-cell adhesion genes, including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL, LEF1, and NSCL/P. Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children. Four common maternal exposures including maternal smoking, environmental tobacco smoke, alcohol consumption and multivitamin supplementation during pregnancy were included in this study.


RESULTS
A total of 226 SNP markers were tested after quality control in this study. Although 23 SNPs in three genes (CTNNB1, CDH1, ACTN1) showed nominal significant association with NSCL/P in the TDT (P<0.05).There were no significant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P>0.000 2). Tests for gene-environment interaction yielded significant results between rs743127 in ACTN1 and environmental tobacco smoke (P=0.000 1) with an estimated OR (case|G and E)=2.00(95%CI: 1.23-3.26) and OR (case|G no E)=0.59 (95%CI: 0.38-0.90). Among the lower P value results in gene-environment tests, there were no significant results between rs1475034, rs370535, rs2273419 in ACTN1, rs106871 in CTNNB1 and environmental tobacco smoke interaction. There were also no significant results between rs7634000, rs2971366, rs2634553, rs1489032, rs7624812 in PVRL3 and multivitamin supplementation during pregnancy in gene-environment tests(P>0.000 2).


CONCLUSIONS
There is no association between cell-cell adhesion genes, including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL, LEF1, and NSCL/P when the genes are considered alone. But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
Y
Y
Yuan
Department of Statistics and Information, Beijing Center for Disease Prevention and Control, Beijing 100013, China.
P
P
Wang
Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan 33305, China.
Y H
YH
Wu-Chou
Department of Pediatric Dentistry, Wuhan University School of Stomatology, Wuhan 430079, China; Mount Sinai Medical Center, New York 10029, USA.
X Q
XQ
Ye
Department of Medical Genetics, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China.
S Z
SZ
Huang
Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu 610041, China.
B
B
Shi
Department of Oral Surgery,Qingdao University Medical College, Qingdao 266000, Shandong, China.
K
K
Wang
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
Z Q
ZQ
Wang
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
D J
DJ
Liu
Peking University School of Basic Medical Sciences, Beijing 100191, China.
Z F
ZF
Wang
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
T
T
Wu
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
H
H
Wang
D044466:Asian People / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics*; D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D018811:Maternal Exposure; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy