Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes:: Risk of placental abruption
Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes:: Risk of placental abruption
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DOI：
10.1016/j.ymgme.2007.02.004
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发表时间：
2007-05-01
影响因子：
3.8
通讯作者：
Rozen, Rima R.
中科院分区：
文献类型：
--
作者：
Ananth, Cande V.;Elsasser, Denise A.;Rozen, Rima R.
目的：蛋氨酸合成酶还原酶(MTRR)和甜菜碱-同型半胱氨酸S甲基转移酶(BHMT)是调节同型半胱氨酸代谢的两种酶。同型半胱氨酸升高(高同型半胱氨酸血症)与不良妊娠结局和血管疾病有关。我们评估了MTRR(66A->；G；I22M)和BHMT(7426->；A；R239Q)的多态是否与早孕相关。我们进一步评估了同型半胱氨酸水平在MTRR和BHMT基因型组和对照组之间的差异。方法：数据来源于新泽西州胎盘早剥研究(NJ-PAS)--这是一项自2002年8月以来正在进行的多中心病例对照研究。临床诊断为早孕的妇女被招募为偶发病例(n=196)，对照(n=191)与基于母亲种族/民族和产次的病例相匹配。对136例患者和136例对照组的血浆总同型半胱氨酸浓度进行了评估。结果：MTR微等位基因频率在病例组和对照组分别为40.8%和42.2%(调整OR0.79，95%CI 0.45，1.40)。BHMT的符合率分别为33.9%和31.7%(调整后OR1.93，95%CI 0.99，4.09)。MtrR纯合子突变形式在病例组和对照组中的分布相似(OR1.18，95%CI 0.62，2.24)。病例组BHMT纯合子突变型频率是对照组的2.8倍(OR2.82，95%CI 1.84，4.97)。基于母亲种族的分层分析没有发现任何关联模式。结论：在该人群中，BHMT(7426->；A)纯合子突变形式与胎盘早剥风险增加之间存在关联。(C)2007 Elsevier Inc.保留所有权利。
Objectives: Methionine synthase reductase (MTRR) and betaine-homocysteine S-methyltransferase (BHMT) are two enzymes that regulate homocysteine metabolism. Elevated homocysteine (hyperhomocysteinemia) is associated with adverse pregnancy outcomes and vascular disease. We assessed whether polymorphisms in MTRR (66A -> G; I22M) and BHMT (7426 -> A; R239Q) were associated with abruption. We further evaluated whether homocysteine levels differed between cases and controls for MTRR and BHMT genotypes.Methods: Data were derived from the New Jersey Placental Abruption Study (NJ-PAS)-an ongoing, multicenter, case-control study since August 2002. Women with a clinical diagnosis of abruption were recruited as incident cases (n = 196), and controls (n = 191) were matched to cases based on maternal race/ethnicity and parity. Total plasma homocysteine concentrations were evaluated in a subset of 136 cases and 136 controls. DNA was genotyped for the MTRR and BHMT polymorphisms.Results: Frequencies of the minor allele of MTRR were 40.8% and 42.2% in cases and controls, respectively (adjusted OR 0.79, 95% CI 0.45, 1.40). The corresponding rates for BHMT were 33.9% and 31.7%, respectively (adjusted OR 1.93, 95% CI 0.99, 4.09). Distributions for the homozygous mutant form of MTRR were similar between cases and controls (OR 1.18, 95% CI 0.62, 2.24). The rate of homozygous mutant BHMT genotype was 2.8-fold (OR 2.82, 95% CI 1.84, 4.97) higher in cases than controls. Stratification of analyses based on maternal race did not reveal any patterns in association.Conclusions: In this population, there was an association between the homozygous mutant form of BHMT (7426 -> A) polymorphism and increased risk for placental abruption. (C) 2007 Elsevier Inc. All rights reserved.