Genome-wide association and gene-environment interaction study identifies variants in ALDH2 associated with serum ferritin in a Chinese population

Gene. 2019 Feb 15:685:196-201. doi: 10.1016/j.gene.2018.11.001. Epub 2018 Nov 3.

Abstract

Ferritin is not only a biomarker of total iron status and systemic inflammation but is also associated with metabolic disorders. A number of genetic variations have been identified to affect serum ferritin, but there is limited understanding of the genetic variations in serum ferritin. To evaluate the relationships among genetic variations, metabolism and ferritin, we performed a secondary analysis of our previous genome-wide association study of ferritin. After adjusting for population stratification and age, the rs671 in ALDH2 was significantly associated with ferritin concentrations (P-combined = 2.98 × 10-8). Men carrying the mutated genotype of rs671 had lower serum ferritin levels. BMI was the mediation between rs671 and ferritin (P = 0.003). Moreover, a significant interaction between rs671 and alcohol consumption on ferritin levels was observed (P = 3.02 × 10-4). rs671 genotypes were significantly relevant to serum ferritin in drinkers (P = 2.39 × 10-7). We reported that rs671 was associated with ferritin in a manner of BMI mediation. These findings will provide new insights into the impacts of genetic variations and metabolisms on serum ferritin levels.

Keywords: ALDH2; Ferritin; Genome-wide association study; Single nucleotide polymorphisms; rs671.

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking
  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • Asian People* / genetics
  • Female
  • Ferritins / blood*
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • Ferritins
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial