A case-parent triad assessment of folate metabolic genes and the risk of childhood acute lymphoblastic leukemia.
A case-parent triad assessment of folate metabolic genes and the risk of childhood acute lymphoblastic leukemia.
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DOI：
10.1007/s10552-012-0058-z
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发表时间：
2012-11
影响因子：
2.3
通讯作者：
Scheurer, Michael E.
中科院分区：
文献类型：
--
作者：
Lupo, Philip J.;Nousome, Darryl;Kamdar, Kala Y.;Okcu, M. Fatih;Scheurer, Michael E.
我们进行了一项病例-父母三联研究，评估叶酸代谢途径中母亲和子女基因型对儿童急性淋巴细胞白血病（ALL）风险的作用。从德克萨斯儿童医院招募儿童ALL病例-父母三联体（N = 120）。使用Sequenom iPLEX MassARRAY对6种叶酸代谢途径基因（MTHFR、MTRR、MTR、DHFR、BHMT和TYMS）中的68个tagSNP对DNA样品进行基因分型。采用对数线性模型分析母亲和子女基因型与ALL之间的关系。在控制错误发现率（<0.1）后，在以下基因中有20个显著的母体效应：BHMT（N = 3）、MTR（N = 12）和TYMS（N = 5）。例如，BHMT rs 558133（相对风险[RR] = 0.51，95%置信区间[CI]：0.30-0.87，P = 0.008，Q = 0.08）和MTR rs 2282369（RR = 0.46，95% CI：0.27-0.80，P = 0.004，Q = 0.08）的母亲基因型与ALL相关。在控制了错误发现率后，没有显著的后代效应。这是为数不多的在儿童ALL风险背景下评估母体遗传效应的研究之一。此外，我们采用了一个家庭为基础的设计，是不太容易受到人口分层的偏见，估计母体遗传效应。我们的研究结果表明，母亲在叶酸代谢途径的遗传变异是相关的儿童急性淋巴细胞白血病的病因。观察到的母体遗传效应支持继续研究子宫环境如何影响ALL风险的必要性。
We conducted a case-parent triad study evaluating the role of maternal and offspring genotypes in the folate metabolic pathway on childhood acute lymphoblastic leukemia (ALL) risk. Childhood ALL case-parent triads (N = 120) were recruited from Texas Children’s Hospital. DNA samples were genotyped using the Sequenom iPLEX MassARRAY for 68 tagSNPs in six folate metabolic pathway genes (MTHFR, MTRR, MTR, DHFR, BHMT, and TYMS). Log-linear modeling was used to examine the associations between maternal and offspring genotypes and ALL. After controlling for the false discovery rate (<0.1), there were 20 significant maternal effects in the following genes: BHMT (N = 3), MTR (N = 12), and TYMS (N = 5). For instance, maternal genotypes for BHMT rs558133 (relative risk [RR] = 0.51, 95% confidence interval [CI]: 0.30–0.87, P = 0.008, Q = 0.08) and MTR rs2282369 (RR = 0.46, 95% CI: 0.27–0.80, P = 0.004, Q = 0.08) were associated with ALL. There were no significant offspring effects after controlling for the false discovery rate. This is one of the few studies conducted to evaluate maternal genetic effects in the context of childhood ALL risk. Furthermore, we employed a family-based design that is less susceptible to population stratification bias in the estimation of maternal genetic effects. Our findings suggest that maternal genetic variation in the folate metabolic pathway is relevant in the etiology of childhood ALL. The observed maternal genetic effects support the need for continued research of how the uterine environment may influence risk of ALL.
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影响因子：
3
作者：
Agopian AJ;Mitchell LE
通讯作者：
Mitchell LE
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
20.3
作者：
Skibola, CF;Smith, MT;Morgan, GJ
通讯作者：
Morgan, GJ
DOI：
10.1073/pnas.94.7.3290
发表时间：
1997-04-01
影响因子：
11.1
作者：
Blount, BC;Mack, MM;Ames, BN
通讯作者：
Ames, BN
影响因子：
30.8
作者：
Papaemmanuil E;Hosking FJ;Vijayakrishnan J;Price A;Olver B;Sheridan E;Kinsey SE;Lightfoot T;Roman E;Irving JA;Allan JM;Tomlinson IP;Taylor M;Greaves M;Houlston RS
通讯作者：
Houlston RS