Identification of three novel loci of ALDH2 Gene for Serum Folate levels in a Male Chinese Population by Genome-Wide Association Study.
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.
['Deng|Caiwang|C|', 'Tang|Shaomei|S|', 'Huang|Xiaoliang|X|', 'Gao|Jiamin|J|', 'Tian|Jiarong|J|', 'Zhou|Xianguo|X|', 'Xie|Yuanliang|Y|', 'Liao|Ming|M|', 'Mo|Zengnan|Z|', 'Wang|Qiuyan|Q|']
D000328:Adult D000071396:Aldehyde Dehydrogenase, Mitochondrial D002681:China D005492:Folic Acid D059647:Gene-Environment Interaction D056426:Genetic Loci D055106:Genome-Wide Association Study D006801:Humans D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide
Genome-wide association rs671 rs4646776 ALDH2, rs3782886 Folic acid