The association of VANGL1 gene polymorphisms and neural tube defects in Han population of northern China

Abstract

Objective To study the association of single nucleotide polymorphisms （SNPs） of the VANGL1 gene and neural tube defects （NTDs） in the Han population of northern China. Methods The SNPs were genotyped and sequenced by polymerase chain reaction （PCR） in 135 NTD patients and paired normal controls. The genotypes and allele frequencies were calculated and analyzed to ex- amine the correlation between VANGL1 SNPs and NTDs. Prediction of 3-D protein structure was conducted by CPHmodels platform. Results We found two nonsynonymous SNPs in the VANGL1 gene which lead to amino acid changes （rs4839469 c. 346G〉A p. A1a116Thr; rs34059106 c. 1040A〉 C p. Glu347Ala）. Both G〉A （Alal16Thr） and G~C （Alal16Pro） polymorphisms at codon 116 of VANGL1 gene were identified. Significant associations were found between the VANGL1 codon 116 polymorphism and NTDs （P = 0. 036 and 0. 010 for allele and genotype frequencies, respectively）. The odd ratio of the GC genotype was 9. 750. The 3-D protein structure prediction showed that the VANGL1 gene codon 116 Pro mutant had shortened a-helix than that of wild type. The Glu347Ala va- riant was not detected in both groups. Conclusions The rs4839469, not the rs34059106 of VANGL1 is associated with NTDs in Han population of northern China. The GC genotype may increase risk for NTDs. Key words: Neural tube defects; VANGL1 gene; Polymorphisms, single nucleotide