Novel evidence of association with nonsyndromic cleft lip with or without cleft palate was shown for single nucleotide polymorphisms in FOXF2 gene in an Asian population.
BACKGROUND
The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts.


METHODS
Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK.


RESULTS
Statistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively.


CONCLUSIONS
Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
Lingxue
L
Bu
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.|National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China.
Qianqian
Q
Chen
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.|Ministry of Health KeyLaboratory of Reproductive Health, Beijing, China.
Hong
H
Wang
Division of Biology and Biomedical Sciences, Washington University, St. Louis, Missouri.
Tianxiao
T
Zhang
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Jacqueline B
JB
Hetmanski
Mathematical Institute, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
Holger
H
Schwender
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Margaret
M
Parker
Department of Medical Research, Chang Gung Memorial Hospital, Taipei, Taiwan.
Yah-Huei Wu
YH
Chou
Department of Plastic Surgery, K K Women's and Children's Hospital, Singapore.
Vincent
V
Yeow
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.
Samuel S
SS
Chong
Department of Biomedical Engineering, Xi'an JiaoTong University, Xi'an, China.
Bo
B
Zhang
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ethylin Wang
EW
Jabs
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Alan F
AF
Scott
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Terri H
TH
Beaty
D000328:Adult; D000818:Animals; D044466:Asian People; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D051381:Rats
C486413:FOXF2 protein, human; D051858:Forkhead Transcription Factors
FBAT; FOXF2; PLINK; SNP; nonsyndromic cleft lip with or without cleft palate; transmission disequilibrium test