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Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate
Author(s) -
Wang Mengying,
Liu Dongjing,
Schwender Holger,
Wang Hong,
Wang Ping,
Zhou Zhibo,
Li Jing,
Wu Tao,
Zhu Hongping,
Beaty Terri H.
Publication year - 2018
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12879
Subject(s) - single nucleotide polymorphism , genetics , multifactor dimensionality reduction , snp , gene , medicine , genome wide association study , biology , genotype
Objective Multiple studies have suggested nonsyndromic cleft lip with or without cleft palate (NSCL/P), and lung cancer may have common genetic etiology. Previous studies have showed genetic variants in nicotinic cholinergic receptor genes ( CHRNs ) may influence risk of lung cancer. We aimed to explore the effect of CHRNs on risk of NSCL/P considering gene–gene (GxG) interaction for these genes. Subjects and Methods We selected 120 markers in 14 CHRNs to test for GxG interaction using 806 Chinese case–parent trios recruited from an international consortium established for a GWAS of oral clefts. Results Totally, two pairs of SNPs yielded significant GxG interactions after Bonferroni correction (rs935865 and rs2337980 with p  =   4.04 × 10 −5 , rs2741335 and rs3743077 with p  =   4.80 × 10 −4 ), and these pairwise interactions were confirmed in permutation tests. In addition, the relative risk (RR) of the putative interaction between rs935865 and rs2337980 was 1.10 (95% CI: 0.92~1.31). Conclusions While the single SNP association and the gene–environment interaction analysis of 14 CHRN genes yielded no signal, this study did demonstrate the importance of considering potential GxG interaction for exploring etiology of NSCL/P. This study suggests an important role for particular combinations of SNPs in CHRN genes in influencing risk to NSCL/P, which needs further study.

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