亚甲基四氢叶酸还原酶基因的两种多态性与胎盘早剥之间的关联。
Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption.
作者信息
Ananth Cande V, Peltier Morgan R, De Marco Celeste, Elsasser Denise A, Getahun Darios, Rozen Rima, Smulian John C
机构信息
Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA.
出版信息
Am J Obstet Gynecol. 2007 Oct;197(4):385.e1-7. doi: 10.1016/j.ajog.2007.06.046.
OBJECTIVE
Heritable thrombophilias have been implicated as a potential cause of abruption by vascular disruption at the uteroplacental interface. Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been linked to vascular complications outside of pregnancy, which includes stroke. Given the underlying thrombotic nature of abruption, we hypothesized that polymorphisms in the MTHFR gene are associated with abruption.
STUDY DESIGN
We examined 2 variants in MTHFR: 677C-->T and 1298A-->C in genomic DNA extracted from maternal blood from the New Jersey-Placental Abruption Study, an ongoing, multicenter case-controlled study. We identified 195 women with a clinical diagnosis of abruption (cases) and 189 control subjects who were matched on race/ethnicity and parity. We assessed allele and genotype frequencies and their associations with abruption risk after adjusting for confounders through multivariable logistic regression analysis.
RESULTS
The wild-type allele (C) frequency of the 677C-->T variant of MTHFR among cases and control subjects was 69.0% and 64.3%, respectively; the wild-type allele (A) of the 1298A-->C variant was 75.9% and 79.4%, respectively. Distributions of the 677C-->T alleles among control subjects violated the Hardy-Weinberg equilibrium (P = .007); distributions of the 1298A-->C alleles were in equilibrium (P = .825). In comparison to the wild-type genotype (C/C), the homozygous mutant form (T/T) of 677C-->T was not associated with abruption (odds ratio, 0.60; 95% confidence interval [CI], 0.33-1.18). Similarly, the homozygous mutant form (C/C) of the 1298A-->C polymorphism was distributed equally between cases and control subjects (odds ratio, 2.28; 95% CI, 0.82-6.35). Plasma homocysteine and vitamin B12, but not folate, concentrations were elevated in cases compared with control subjects among women with the wild-type genotype of MTHFR 677C-->T (P = .039 for homocysteine; P = .048 for B12; P = .224 for folate).
CONCLUSION
In this population, neither heterozygosity nor homozygosity for the 677C-->T and 1298A-->C variants in MTHFR was associated with placental abruption.
目的
遗传性血栓形成倾向被认为是子宫胎盘界面血管破裂导致胎盘早剥的一个潜在原因。亚甲基四氢叶酸还原酶（MTHFR）基因多态性与妊娠以外的血管并发症有关，其中包括中风。鉴于胎盘早剥潜在的血栓形成本质，我们推测MTHFR基因多态性与胎盘早剥相关。
研究设计
我们在新泽西胎盘早剥研究中，对从母血中提取的基因组DNA中的MTHFR的2个变异体进行检测：677C→T和1298A→C，这是一项正在进行的多中心病例对照研究。我们确定了195例临床诊断为胎盘早剥的女性（病例组）和189名在种族/民族和胎次上匹配的对照者。我们评估了等位基因和基因型频率，并通过多变量逻辑回归分析在调整混杂因素后评估它们与胎盘早剥风险的关联。
结果
MTHFR的677C→T变异体的野生型等位基因（C）在病例组和对照组中的频率分别为69.0%和64.3%；1298A→C变异体的野生型等位基因（A）分别为75.9%和79.4%。对照组中677C→T等位基因的分布违反了哈迪-温伯格平衡（P = 0.007）；1298A→C等位基因的分布处于平衡状态（P = 0.825）。与野生型基因型（C/C）相比，677C→T的纯合突变形式（T/T）与胎盘早剥无关（优势比，0.60；95%置信区间[CI]，0.33 - 1.18）。同样，1298A→C多态性的纯合突变形式（C/C）在病例组和对照组中的分布相同（优势比，2.28；95% CI，0.82 - 6.35）。在MTHFR 677C→T野生型基因型的女性中，病例组的血浆同型半胱氨酸和维生素B12浓度升高，但叶酸浓度未升高（同型半胱氨酸P = 0.039；维生素B12 P = 0.048；叶酸P = 0.224）。
结论
在该人群中，MTHFR的677C→T和1298A→C变异体的杂合性和纯合性均与胎盘早剥无关。
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