Instituto Nacional de Salud Pública, Av. Universidad 655, Col. Santa María Ahuacatitlán, C.P. 62100, Cuernavaca, Morelos, México.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Environ Res. 2018 Jul;164:18-23. doi: 10.1016/j.envres.2018.01.050. Epub 2018 Feb 17.
Nutrients and genetic polymorphisms participating in one-carbon metabolism may explain interindividual differences in inorganic arsenic (iAs) methylation capacity, which in turn may account for variations in susceptibility to iAs-induced diseases.
Women (n = 1027) exposed to iAs in Northern Mexico were interviewed. Blood and urine samples were collected. Nutrient dietary intake was estimated using a validated food frequency questionnaire. iAs methylation capacity was calculated from urinary iAs species (iAs, monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) measured by high performance liquid chromatography (HPLC-ICP-MS). One polymorphism in each of the five genes evaluated was genotyped by allelic discrimination. Multivariable linear regression models were used to evaluate if genetic polymorphisms modified the associations between iAs methylation capacity parameters and nutrient intake.
The median (min-max) concentration of total arsenic (TAs) was 20.2 (1.3-2776.0) µg/g creatinine in the study population. Significant interactions for iAs metabolism were only found with FOLH1 c.223 T > C polymorphism and vitamin B12 intake, so that CT and CC genotype carriers had significantly lower %iAs, and higher DMA/iAs with an increased vitamin B12 intake, as compared to carriers of wild-type TT.
Differences in dietary nutrient intake and genetic variants in one-carbon metabolism may jointly influence iAs methylation capacity. Confirmation of these interactions in other populations is warranted.
参与一碳代谢的营养素和遗传多态性可能解释了无机砷（iAs）甲基化能力的个体间差异，而这反过来又可能导致对 iAs 诱导疾病的易感性的变化。
1）评估五个一碳代谢基因（FOLH1 c.223T > C、MTHFD1 c.1958G > A、MTHFR c.665C > T、MTR c.2756A > G 和 MTRR c.66A > G）中的多态性与 iAs 甲基化能力之间的关联；2）评估之前报道的营养素摄入与 iAs 甲基化能力之间的关联是否受这些多态性的影响。
对暴露于墨西哥北部 iAs 的女性（n = 1027）进行访谈。采集血液和尿液样本。营养素膳食摄入量通过验证的食物频率问卷进行评估。通过高效液相色谱-电感耦合等离子体质谱法（HPLC-ICP-MS）测定尿液中的 iAs 物种（iAs、一甲基砷酸 [MMA] 和二甲基砷酸 [DMA]）来计算 iAs 甲基化能力。评估的五个基因中的每个基因都有一个多态性通过等位基因鉴别进行基因分型。多变量线性回归模型用于评估遗传多态性是否改变了 iAs 甲基化能力参数与营养素摄入之间的关联。
研究人群中总砷（TAs）的中位数（最小值-最大值）浓度为 20.2（1.3-2776.0）µg/g 肌酐。仅发现 FOLH1 c.223T > C 多态性与维生素 B12 摄入之间存在 iAs 代谢的显著相互作用，因此与野生型 TT 携带者相比，CT 和 CC 基因型携带者的 %iAs 明显降低，并且随着维生素 B12 摄入的增加，DMA/iAs 升高。
膳食营养素摄入的差异和一碳代谢中的遗传变异可能共同影响 iAs 甲基化能力。需要在其他人群中证实这些相互作用。
