Yang Quan-He, Botto Lorenzo D, Gallagher Margaret, Friedman J M, Sanders Christopher L, Koontz Deborah, Nikolova Stanimila, Erickson J David, Steinberg Karen
National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Am J Clin Nutr. 2008 Jul;88(1):232-46. doi: 10.1093/ajcn/88.1.232.
Abnormalities of folate and homocysteine metabolism are associated with a number of pediatric and adult disorders. Folate intake and genetic polymorphisms encoding folate-metabolizing enzymes influence blood folate and homocysteine concentrations, but the effects and interactions of these factors have not been studied on a population-wide basis.
The objective was to assess the prevalence of these genetic polymorphisms and their relation to serum folate and homocysteine concentrations.
DNA samples from 6793 participants in the third National Health and Nutrition Examination Survey (NHANES III) during 1991-1994 were genotyped for polymorphisms of genes coding for folate pathway enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C, methionine synthase reductase (MTRR) 66A-->G, and cystathionine-beta-synthase 844ins68. The influence of these genetic variants on serum folate and homocysteine concentrations was analyzed by age, sex, and folate intake in 3 race-ethnicity groups.
For all race-ethnicity groups, serum folate and homocysteine concentrations were significantly related to the MTHFR 677C-->T genotype but not to the other polymorphisms. Persons with the MTHFR 677 TT genotype had a 22.1% (95% CI: 14.6%, 28.9%) lower serum folate and a 25.7% (95% CI: 18.6%, 33.2%) higher homocysteine concentration than did persons with the CC genotype. Moderate daily folic acid intake (mean: 150 microg/d; 95% CI: 138, 162) significantly reduced the difference in mean homocysteine concentrations between those with the MTHFR 677 CC and TT genotypes. We found a significant interaction between MTHFR 677C-->T and MTRR 66A-->G on serum homocysteine concentrations among non-Hispanic whites.
The MTHFR 677C-->T polymorphism was associated with significant differences in serum folate and homocysteine concentrations in the US population before folic acid fortification. The effect of MTHFR 677C-->T on homocysteine concentrations was reduced by moderate daily folic acid intake.
叶酸和同型半胱氨酸代谢异常与多种儿科和成人疾病相关。叶酸摄入量以及编码叶酸代谢酶的基因多态性会影响血液中的叶酸和同型半胱氨酸浓度，但尚未在全人群基础上研究这些因素的作用及相互作用。
评估这些基因多态性的患病率及其与血清叶酸和同型半胱氨酸浓度的关系。
对1991 - 1994年第三次全国健康和营养检查调查（NHANES III）中6793名参与者的DNA样本进行基因分型，检测编码叶酸途径酶5,10 - 亚甲基四氢叶酸还原酶（MTHFR）677C→T和1298A→C、甲硫氨酸合成酶还原酶（MTRR）66A→G以及胱硫醚-β-合酶844ins68的基因多态性。在3个种族 - 族裔群体中，按年龄、性别和叶酸摄入量分析这些基因变异对血清叶酸和同型半胱氨酸浓度的影响。
在所有种族 - 族裔群体中，血清叶酸和同型半胱氨酸浓度与MTHFR 677C→T基因型显著相关，与其他多态性无关。与CC基因型者相比，MTHFR 677 TT基因型者的血清叶酸浓度低22.1%（95%CI：14.6%，28.9%），同型半胱氨酸浓度高25.7%（95%CI：18.6%，33.2%）。适度的每日叶酸摄入量（平均：150μg/d；95%CI：138，162）显著降低了MTHFR 677 CC和TT基因型者之间平均同型半胱氨酸浓度的差异。我们发现非西班牙裔白人中，MTHFR 677C→T和MTRR 66A→G对血清同型半胱氨酸浓度存在显著相互作用。
在叶酸强化之前，MTHFR 677C→T多态性与美国人群血清叶酸和同型半胱氨酸浓度的显著差异相关。适度的每日叶酸摄入量可降低MTHFR 677C→T对同型半胱氨酸浓度的影响。
