Detecting Gene-Gene Interaction among DNA Repair Genes in Chinese non-Syndromic Cleft lip with or Without Palate Trios.

OBJECTIVE: The objective of this study is to investigate the gene-gene interactions associated with NSCL/P among DNA repair genes.

DESIGN: This study included 806 NSCL/P case-parent trios from China. Quality control process was conducted for genotyped single nucleotide polymorphisms (SNPs) located in six DNA repair genes ( ATR , ERCC4 , RFC1 , TYMS , XRCC1 and XRCC3 ). We tested gene-gene interactions with Cordell's method using statistical package TRIO in R software. Bonferroni corrected significance level was set as P  = 4.24 × 10-4 . We also test the robustness of the interactions by permutation tests.

SETTING: Not applicable.

PATIENTS/PARTICIPANTS: A total of 806 NSCL/P case-parent trios (complete trios: 682, incomplete trios: 124) with Chinese ancestry.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE(S): Not applicable.

RESULTS: A total of 118 SNPs were extracted for the interaction tests. Fourteen pairs of significant interactions were identified after Bonferroni correction, which were confirmed in permutation tests. Twelve pairs were between ATR and ERCC4 or XRCC3 . The most significant interaction occurred between rs2244500 in TYMS and rs3213403 in XRCC1 ( P  = 8.16 × 10-15 ).

CONCLUSIONS: The current study identified gene-gene interactions among DNA repair genes in 806 Chinese NSCL/P trios, providing additional evidence for the complicated genetic structure underlying NSCL/P. ATR , ERCC4 , XRCC3 , TYMS and RFC1 were suggested to be possible candidate genes for NSCL/P.