Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water.
Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water.
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DOI：
10.1289/ehp.02110729
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发表时间：
2002-07
影响因子：
10.4
通讯作者：
Smith AH
中科院分区：
文献类型：
--
作者：
Chung JS;Kalman DA;Moore LE;Kosnett MJ;Arroyo AP;Beeris M;Mazumder DN;Hernandez AL;Smith AH
我们调查了饮用水中砷对家庭尿甲基化模式的影响。砷甲基化可以通过测量尿中无机砷（InAs）及其甲基化代谢物，甲基胂酸盐（MMA）和二甲基胂酸盐（DMA）的水平来评估。甲基化活性反映在比率中：InAs/甲基化砷（InAs/metAs）和MMA/DMA。来自智利的11个家庭被选中，因为他们长期暴露于饮用水中非常高的砷水平（735-762微克/升）。每个家庭由一位父亲、一位母亲和两个孩子组成。我们测量了每个参与者（n = 44）的尿砷及其甲基化代谢产物。组内相关系数表明，13-52%的甲基化模式的变化是来自一个特定的家庭成员。计算了父亲-母亲、父母-子女和兄弟姐妹对的家庭相关性。校正总尿砷、年龄和性别后，兄弟姐妹间甲基化模式密切相关[InAs/metAs r = 0.78，95%可信区间（CI），0.34-0.94; MMA/DMA r = 0.82，95%CI，0.43-0.95]，而父亲-母亲间的相关性较低（分别为r = 0.18，r =-0.01）。当对特定的血液微量营养素（蛋氨酸、同型半胱氨酸、叶酸、维生素B6、硒和可能与甲基化有关的维生素B12）进行调整时，家族相关性没有明显改变。我们还报告了一个家庭系谱与高患病率的砷引起的影响。来自这个家庭的参与者有低的InAs/metAs值，这与三价甲基化砷物种的毒性增加一致。尽管我们的样本量很小，但我们观察到甲基化模式在家庭中聚集，并且在兄弟姐妹中相关，这为砷甲基化变异的遗传基础提供了证据。需要进行更大规模的研究和更广泛的谱系来证实这些发现。
We investigated the evidence of a familial contribution to urinary methylation patterns in families ingesting arsenic in drinking water. Arsenic methylation can be assessed by measuring urinary levels of inorganic arsenic (InAs) and its methylated metabolites, monomethylarsonate (MMA), and dimethylarsinate (DMA). Methylation activity is reflected in the ratios: InAs/methylated arsenic (InAs/metAs) and MMA/DMA. Eleven families from Chile were selected because of their long-term exposure to very high levels of arsenic in drinking water (735-762 microg/L). Each family consisted of a father, a mother, and two children. We measured urinary arsenic and its methylated metabolites for each participant (n = 44). The intraclass correlation coefficients showed that 13-52% of the variations in the methylation patterns were from being a member of a specific family. Family correlations were calculated for father-mother, parent-child, and sibling-sibling pairs. Methylation patterns correlated strongly between siblings [r = 0.78 for InAs/metAs, 95% confidence interval (CI), 0.34-0.94; r = 0.82 for MMA/DMA, 95%CI, 0.43-0.95] compared to lower correlations in father-mother pairs (r = 0.18, r = -0.01, respectively), after adjustment for total urinary arsenic, age, and sex. Family correlations were not notably altered when adjustments were made for specific blood micronutrients (methionine, homocysteine, folate, vitamin B6, selenium, and vitamin B12 potentially related to methylation. We also report on a family pedigree with high prevalence of arsenic-induced effects. Participants from this family had low InAs/metAs values, which is consistent with increased toxicity of trivalent methylated arsenic species. Despite our small sample size, we observed that methylation patterns aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Larger studies with more extensive pedigrees will need to be conducted to confirm these findings.
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影响因子：
10.4
作者：
Concha, G;Nermell, B;Vahter, M
通讯作者：
Vahter, M
影响因子：
6.7
作者：
SCOTT, MC;VANLOON, JA;WEINSHILBOUM, RM
通讯作者：
WEINSHILBOUM, RM
DOI：
10.1016/s0014-2999(95)80104-9
发表时间：
1995-12-07
期刊：
EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION
影响因子：
--
作者：
VAHTER, M;CONCHA, G;NATARAJAN, AT
通讯作者：
NATARAJAN, AT
影响因子：
2.8
作者：
WEINSHILBOUM, R
通讯作者：
WEINSHILBOUM, R
影响因子：
6.1
作者：
ATALLAH, RH;KALMAN, DA
通讯作者：
KALMAN, DA