Association between single-nucleotide polymorphisms on chromosome 1p22 and 20q12 and nonsyndromic cleft lip with or without cleft palate: New data in Han Chinese and meta-analysis

Authors

  • Enmin Huang,

    1. Cleft Lip and Palate Treatment Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
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    • E.H. and H.C. contributed equally to this work and should be considered co-first authors.

  • Hongqiu Cheng,

    1. Department of Infectious Diseases, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
    2. Hubei University of Chinese Medicine, Wuhan, Hubei, People's Republic of China
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    • E.H. and H.C. contributed equally to this work and should be considered co-first authors.

  • Mingyan Xu,

    1. Cleft Lip and Palate Treatment Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
    2. Department of Stomatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
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  • Shenyou Shu,

    1. Cleft Lip and Palate Treatment Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
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  • Shijie Tang

    Corresponding author
    1. Cleft Lip and Palate Treatment Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
    • Cleft Lip and Palate Treatment Center, the Second Affiliated Hospital of Shantou University Medical College, North Dong Xia Road, Shantou 515041, Guangdong, People's Republic of China
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  • Part of this paper will be presented at the 69th Annual Meeting of the American Cleft Palate-Craniofacial Association in San Jose, California, April 17–21, 2012.

  • Supported by a grant from the National Science Foundation for Young Scientists of China (grant no. 81001284).

Abstract

BACKGROUND

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital malformation associated with genetic and environmental risk factors. A recent genome-wide association study identified two novel susceptibility loci on chromosomes 1p22 and 20q12; however, conflicting results, especially for 1p22, have been reported in Han Chinese population. The aims of this study were to replicate this association with risk of NSCL/P in the southern Han Chinese population and to discern the effect of these loci by a meta-analysis.

METHODS

To this end, 305 patients with NSCL/P, 356 phenotypically normal controls, and an additional 176 case-parent trios were recruited. Four of the previously associated single nucleotide polymorphisms (SNPs) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Furthermore, two published datasets were combined with the present results to determine the precise roles of the loci.

RESULTS

SNPs (rs6072081, rs13041247, and rs6102085) on 20q12 were found to be strongly associated with NSCL/P (Bonferroni-corrected and χ2 test; p values < 0.05). Subsequent analysis of the case-parent trio provided similar results. However, neither the association study nor the trio analysis supported a causative role for SNP rs560426 on 1p22 in NSCL/P susceptibility. Stratified meta- analysis combining Chinese samples supported our findings.

CONCLUSIONS

This cross-validation study confirmed the previous findings that SNPs in 20q12 are associated with NSCL/P in Han Chinese population. We further conclude that rs560426 on 1p22 might not have a major influence on susceptibility to NSCL/P in southern Han Chinese, but future studies with other Han Chinese populations are needed. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.

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