Heritability and preliminary genome-wide linkage analysis of arsenic metabolites in urine.
Heritability and preliminary genome-wide linkage analysis of arsenic metabolites in urine.
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尿液中砷代谢产物的遗传力和初步基因组连接分析。
DOI：
10.1289/ehp.1205305
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发表时间：
2013-03
影响因子：
10.4
通讯作者：
Navas-Acien A
中科院分区：
文献类型：
--
作者：
Tellez-Plaza M;Gribble MO;Voruganti VS;Francesconi KA;Goessler W;Umans JG;Silbergeld EK;Guallar E;Franceschini N;North KE;Kao WH;MacCluer JW;Cole SA;Navas-Acien A
背景：在关联研究中，砷（III）甲基转移酶（AS3MT）与尿砷代谢物有关。其他基因也可能在砷的代谢和排泄中发挥作用。目的：我们从强心脏研究（SHS）中评估美国印第安成年人尿砷代谢物的遗传决定因素。方法：我们在2907名有尿砷测量的SHS参与者和至少一名亲属中评估了尿砷代谢物的遗传性[无机砷百分比（%iAs），单甲基胂酸百分比（%MMA）和二甲基胂酸百分比（%DMA）]。我们对487名参与者进行了初步的连锁分析，这些参与者在大约400个短串联重复标记上具有可用的基因型，使用一般谱系方差成分方法来定位数量性状位点（QTL）。结果：%iAs、%MMA和%DMA的中位数（四分位数范围）分别为7.7%（5.4-10.7%）、13.6%（10.5-17.1%）和78.4%（72.5-83.1%）。估计遗传率%iAs为53%，%MMA为50%，%DMA为59%。在对性别、年龄、吸烟、体重指数、饮酒、地区和尿砷总浓度等因素进行调整后，LOD[比值的对数（以10为基数）]得分提示，与影响5号染色体（%iAs的LOD = 2.03）、9号染色体（%iAs的LOD = 2.05， %MMA的LOD = 2.10）和11号染色体（%iAs的LOD = 1.94）上的尿砷代谢物的qtl存在遗传关联。在AS3MT的2 Mb内，10号染色体上的%DMA峰值的LOD为1.80。结论：这项基于美国印第安社区人群的家庭研究支持遗传对尿液中砷代谢物分布的影响，并且可能涉及AS3MT以外的基因。
Background: Arsenic (III) methyltransferase (AS3MT) has been related to urine arsenic metabolites in association studies. Other genes might also play roles in arsenic metabolism and excretion. Objective: We evaluated genetic determinants of urine arsenic metabolites in American Indian adults from the Strong Heart Study (SHS). Methods: We evaluated heritability of urine arsenic metabolites [percent inorganic arsenic (%iAs), percent monomethylarsonate (%MMA), and percent dimethylarsinate (%DMA)] in 2,907 SHS participants with urine arsenic measurements and at least one relative within the cohort. We conducted a preliminary linkage analysis in a subset of 487 participants with available genotypes on approximately 400 short tandem repeat markers using a general pedigree variance component approach for localizing quantitative trait loci (QTL). Results: The medians (interquartile ranges) for %iAs, %MMA, and %DMA were 7.7% (5.4–10.7%), 13.6% (10.5–17.1%), and 78.4% (72.5–83.1%), respectively. The estimated heritability was 53% for %iAs, 50% for %MMA, and 59% for %DMA. After adjustment for sex, age, smoking, body mass index, alcohol consumption, region, and total urine arsenic concentrations, LOD [logarithm (to the base of 10) of the odds] scores indicated suggestive evidence for genetic linkage with QTLs influencing urine arsenic metabolites on chromosomes 5 (LOD = 2.03 for %iAs), 9 (LOD = 2.05 for %iAs and 2.10 for %MMA), and 11 (LOD = 1.94 for %iAs). A peak for %DMA on chromosome 10 within 2 Mb of AS3MT had an LOD of 1.80. Conclusions: This population-based family study in American Indian communities supports a genetic contribution to variation in the distribution of arsenic metabolites in urine and, potentially, the involvement of genes other than AS3MT.
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DOI：
10.1016/j.mrfmmm.2008.07.003
发表时间：
2009-07-10
影响因子：
2.3
作者：
Engstrom, Karin Schlawicke;Nermell, Barbro;Broberg, Karin
通讯作者：
Broberg, Karin
影响因子：
3.6
作者：
Baccarelli A;Bollati V
通讯作者：
Bollati V
DOI：
10.1097/ede.0b013e3181812bb7
发表时间：
2008-09
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Franklin M;Koutrakis P;Schwartz P
通讯作者：
Schwartz P
影响因子：
2.6
作者：
Hernandez, Alba;Xamena, Noel;Marcos, Ricardo
通讯作者：
Marcos, Ricardo
影响因子：
3.8
作者：
Chen, Baowei;Arnold, Lora L.;Le, X. Chris
通讯作者：
Le, X. Chris