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

Tao, Yuting, Huang, Xiaoliang, Xie, Yuanliang, Zhou, Xianguo, He, Xiaoli, Tang, Shaomei, Liao, Ming, Chen, Yang, Tan, Aihua, Chen, Yingchun, Wang, Qiuyan, Mo, Zengnan
Gene 2019 v.685 pp. 196-201
alcohol drinking, biomarkers, blood serum, body mass index, ferritin, genetic variation, genome-wide association study, genotype, genotype-environment interaction, inflammation, iron, men, metabolic diseases, metabolism
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.