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A Genetic Variant in FIGN Gene Reduces the Risk of Congenital Heart Disease in Han Chinese Populations

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Congenital heart disease (CHD) is one of the most common birth anomalies worldwide. Folate deficiency is an independent risk factor for CHD. Genome-wide association studies (GWAS) revealed that human folate… Click to show full abstract

Congenital heart disease (CHD) is one of the most common birth anomalies worldwide. Folate deficiency is an independent risk factor for CHD. Genome-wide association studies (GWAS) revealed that human folate level could be significantly influenced by fidgetin (FIGN), methylenetetrahydrofolate reductase (MTHFR), prickle homolog 2 (PRICKLE2), synaptotagmin 9 (SYT9), gamma-aminobutyric acid B receptor 2 (GABBR2), and alkaline phosphatase (ALPL) genes. The association between the above-mentioned six variants and CHD was examined in the two independent case-control studies in a total of 868 CHD patients and 931 healthy controls. Our results showed that the G > C (rs2119289) variant in intron 4 of FIGN led to a significant reduction of CHD susceptibility in both the separate and combined case-control studies (allele distribution P < 0.001, genotype distribution P < 0.001). Specifically, by analyzing the combined samples, we observed that the risks of CHD in individuals carrying the heterozygous G/C and homozygous C/C genotypes were reduced by 45% (adjusted OR 0.55, 95% CI 0.47–0.67) and 66% (adjusted OR 0.34, 95% CI 0.23–0.50), respectively, in comparison with individuals carrying the wild-type G/G genotype. Our findings have demonstrated that the C allele of variant rs2119289 of FIGN gene is an important genetic marker for decreased CHD risk. Considering that the rs2119289 of FIGN gene is related to the appropriate folate level, FIGN might play an important role in CHD by upregulating plasma folate concentration during embryo heart development. This work provides a new insight for risk assessment of CHD.

Keywords: fign gene; congenital heart; chd; fign

Journal Title: Pediatric Cardiology
Year Published: 2017

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