Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

Abstract

This study aimed to investigate possible associations of the susceptibility to congenital heart defects (CHDs) with AXIN1 rs1805105, rs12921862 and rs370681 gene variants and haplotypes, and AXIN2 rs2240308 gene variant. Significant associations were identified for AXIN1 rs370681 and AXIN2 rs2240308 variants. AXIN1 rs370681 variant was significantly associated with decreased odds of CHDs (adjusted OR varying from 0.13 to 0.28 in codominant, dominant and recessive gene models), while the AXIN2 rs2240308 variant was associated with increased odds of CHD in the dominant model. The haplotype-based generalized linear model regression of AXIN1 rs1805105, rs12921862 and rs370681 variants revealed that C-C-C and C-C-T haplotypes significantly increased the risk of CHDs (p < 0.05). No significant second order epistatic interactions were found between investigated variants (AXIN1 rs1805105, rs12921862, rs370681, and AXIN2 rs2240308). Our conclusion is that AXIN1 rs1805105, rs12921862, and rs370681 (C-C-C and C-C-T) haplotypes and AXIN2 rs2240308 contribute to CHDs susceptibility.

Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes

“…The variants in these genes could increase the risk of developing FASD in a PAE individual given their potential to cause similar facial features as seen in children with FASD. Six significant variants within AXIN1, AXIN2, CAV1, GLI1, RYR2, and SFRP4 genes were discovered that have an impact on heart development and function [52][53][54][55][56], which could worsen cardiac malformations in FASD individuals. Four significant variants in the BMP2, WNT10B, and WNT16 genes were found and could have an impact on bone mineral density, ossification defects, or increased risk of bone fracture [57][58][59][60].…”