Identification of three novel loci of ALDH2 Gene for Serum Folate levels in a Male Chinese Population by Genome-Wide Association Study

Gene. 2018 Oct 20:674:121-126. doi: 10.1016/j.gene.2018.06.080. Epub 2018 Jun 25.

Abstract

Background: Serum folate is important in clinical researches and DNA synthesis and methylation. Some loci and genes that are associated with folate levels had been detected by genome-wide association studies (GWAS), such as rs1801133 in MTHFR and rs1979277 in SHMT1. Nevertheless, only a small part of variants has been clearly identified for serum folate. Hence, we conducted a GWAS to discover new inherited susceptibility and gene-environment interactions on serum folate concentration.

Materials and methods: In a healthy Chinese population of 1999 men, genotyping was performed using Illumina HumanOmni1-Quad BeadChip. Serum folate levels were measured by enzyme-linked immunosorbent assay (ELISA), pathway enrichment analysis and statistical analysis were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Statistic Package for Social Science (SPSS).

Results: We validated that rs1801133 in MTHFR was significantly involved in serum folate (P = 4.21 × 10-19). Surprisingly, we discovered three novel loci rs3782886, rs671, and rs4646776 of ALDH2 gene were suggestively significantly associated with folate serum folate levels in the male population studied (P = 2.17 × 10-7, P = 3.60 × 10-7, P = 3.99 × 10-7, respectively) after adjusting for population stratification, BMI and age. Men with the AA genotype had significantly higher serum folate levels compared with men with the GG/AG genotype. But we found ALDH2 gene mutation no relation to part of environmental factors on serum folate levels.

Conclusion: In a male Chinese population, genome-wide association study discovered that three novel SNPs rs3782886, rs671 and rs4646776 of ALDH2 gene were suggestively significantly associated with serum folate levels.

Keywords: ALDH2, rs3782886; Folic acid; Genome-wide association; rs4646776; rs671.

MeSH terms

  • Adult
  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • China
  • Folic Acid / blood*
  • Gene-Environment Interaction
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • Folic Acid
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial