Nurk E, Tell G S, Refsum H, Ueland P M, Vollset S E
Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
QJM. 2006 May;99(5):289-98. doi: 10.1093/qjmed/hcl040. Epub 2006 Apr 13.
The factor V Leiden (FVL) mutation is the most common cause of inherited thrombophilia in Caucasian populations, and women with this variant allele are at increased risk for pregnancy complications.
To examine whether the FVL allele is associated with pregnancy complications and adverse outcomes in a population-based study, and to identify potential factors that interact with the FVL genotype.
Retrospective cohort study in a geographically-defined area.
Polymorphisms of factor V 1691G-->A, methylenetetrahydrofolate reductase (MTHFR) 677C --> T and 1298A --> C and plasma levels of total homocysteine, folate and vitamin B(12) were determined in blood samples collected in 1992-1993 from 5874 women aged 40-42 years, and linked with 14 474 pregnancies in the same women, recorded in the Medical Birth Registry of Norway, 1967-1996.
The allelic frequency of FVL was 3.7% (6.9% heterozygotes, 0.3% homozygotes). Maternal FVL mutation was associated with significantly higher risks of pre-eclampsia (OR 1.63, 95%CI 1.15-2.30), pre-eclampsia at <37 weeks (OR 2.76, 1.34-5.70), low birth weight (OR 1.34, 95%CI 1.03-1.74) and stillbirth (OR 2.20, 95%CI 1.45-3.36). The presence of a variant allele for the 677C --> T MTHFR polymorphism strengthened the association between FVL and stillbirth (OR 3.34, 95%CI 1.95-5.73) (p(interaction) = 0.034).
FVL mutation is a significant risk factor for pregnancy complications and adverse outcomes, and MTHFR 677CT/TT genotype can further enhance the risk of stillbirth.
因子V莱顿（FVL）突变是白种人群中遗传性易栓症最常见的病因，携带这种变异等位基因的女性发生妊娠并发症的风险增加。
在一项基于人群的研究中，检验FVL等位基因是否与妊娠并发症及不良结局相关，并确定与FVL基因型相互作用的潜在因素。
在一个地理区域内进行的回顾性队列研究。
对1992 - 1993年采集的5874名40 - 42岁女性的血样，测定因子V 1691G→A、亚甲基四氢叶酸还原酶（MTHFR）677C→T和1298A→C的多态性以及总同型半胱氨酸、叶酸和维生素B12的血浆水平，并将其与这些女性在1967 - 1996年挪威医疗出生登记处记录的14474次妊娠情况相联系。
FVL的等位基因频率为3.7%（杂合子为6.9%，纯合子为0.3%）。母亲FVL突变与子痫前期（比值比1.63，95%可信区间1.15 - 2.30）、孕周<37周的子痫前期（比值比2.76，1.34 - 5.70）、低出生体重（比值比1.34，95%可信区间1.03 - 1.74）和死产（比值比2.20，95%可信区间1.45 - 3.36）的风险显著升高相关。677C→T MTHFR多态性的变异等位基因的存在加强了FVL与死产之间的关联（比值比3.34，95%可信区间1.95 - 5.73）（交互作用p = 0.034）。
FVL突变是妊娠并发症和不良结局的一个重要风险因素，MTHFR 677CT/TT基因型可进一步增加死产风险。
