Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China; Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Gene. 2018 Oct 20;674:121-126. doi: 10.1016/j.gene.2018.06.080. Epub 2018 Jun 25.
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.
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).
We validated that rs1801133 in MTHFR was significantly involved in serum folate (P = 4.21 × 10). 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, P = 3.60 × 10, P = 3.99 × 10, 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.
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.
血清叶酸在临床研究、DNA 合成和甲基化中非常重要。全基因组关联研究（GWAS）已经发现了一些与叶酸水平相关的基因座和基因，例如 MTHFR 中的 rs1801133 和 SHMT1 中的 rs1979277。然而，只有一小部分变体被明确确定为血清叶酸。因此，我们进行了 GWAS，以发现新的遗传性易感性和基因-环境相互作用对血清叶酸浓度的影响。
在一个由 1999 名男性组成的健康中国人群中，使用 Illumina HumanOmni1-Quad BeadChip 进行基因分型。通过酶联免疫吸附试验（ELISA）测量血清叶酸水平，通过数据库注释、可视化和综合发现（DAVID）和社会科学统计软件包（SPSS）进行途径富集分析和统计分析。
我们验证了 MTHFR 中的 rs1801133 与血清叶酸显著相关（P=4.21×10）。令人惊讶的是，我们发现 ALDH2 基因中的三个新的 rs3782886、rs671 和 rs4646776 位点与所研究的男性人群中的叶酸血清叶酸水平呈显著相关（分别为 P=2.17×10、P=3.60×10、P=3.99×10），经过人群分层、BMI 和年龄调整后。与 GG/AG 基因型的男性相比，AA 基因型的男性血清叶酸水平显著更高。但是，我们发现 ALDH2 基因突变与部分环境因素对血清叶酸水平无关系。
在中国男性人群中，全基因组关联研究发现 ALDH2 基因的三个新的 rs3782886、rs671 和 rs4646776 单核苷酸多态性与血清叶酸水平显著相关。
