Abstract: Objective To identify the impact of gene-gene interaction between VANGL1, FZD3 and FZD6 on the risk of neural tube defects in Han population of Northern China. Methods Two SNPs (rs4 839 469 and rs34 059 106) within VANGL1, two SNPs (rs2 241 802 and rs28 639 533) within FZD3 and three SNPs(rs827 528, rs3 808 553 and rs12 549 394) within FZD6 were genotyped in 135 NTD patients and 135 healthy controls．The gene-gene interaction between VANGL1, FZD3 and FZD6 was analyzed by Multifactor Dimensionality Reduction software. Results The frequency of genotypes of rs4 839 469 within VANGL1 and rs3 808 553 within FZD6 were significantly higher in patients than that in controls(P<0.05)．MDR revealed that the significance were shown in patterns with 2 SNPs (rs4 839 469—rs3 808 553)(OR=3.18，95% CI:1.85～5.44；χ2=18.39，P<0.0001)，3 SNPs( rs4 839 469—rs2 241 802—rs3 808 553) (OR=4.17，95% CI:2.43～7.14；χ2=28.5，P<0.0001)and 4 SNPs(rs4 839 469—rs2 241 802—rs827 528—rs3 808 553) (OR=7.34，95% CI:3.98～13.54；χ2=45.3，P<0.0001)．Conclusion The gene-gene interaction between VANGL1, FZD3 and FZD6 may exist and increase the risk for NTDs.

Key words: VANGL1 gene, FZD3 gene, FZD6 gene, gene-gene interaction, neural tube defects