MTHFR基因多态性与妊娠高血压综合征的相关性研究

目的:探讨N5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性在妊娠期高血压疾病发病中的作用地位。方法:PCR-RFLP检测54例妊娠期高血压疾病患者与125例对照组患者MTHFRC677T及A1298C基因多态性。结果:病例组MTHFRC677TC/T基因型频率显著高于正常对照组,总突变T等位基因频率也显著高于对照组(P<0.05);病例组MTHFRA1298C三种基因型频率与对照组比较差异无显著性。结论:MTHFR基因C677T多态性可能是妊娠期高血压疾病的危险因素,可作为该病预后的检测指标;而MTHFR基因A1298C多态性并非妊娠期高血压疾病致病因素。     

ACL(+)复发性流产与亚甲基四氢叶酸还原酶C677T和A1298C位点突变关联的研究

目的:探讨亚甲基四氢叶酸还原酶基因(methylenetetrahydrofolate reductase,MTHFR)C677T和A1298C位点突变与抗心磷脂抗体(anticard iolipin antibody,ACL)阳性复发性流产是否相关。方法:采用聚合酶链式反应-限制性片断长度多态性方法,检测39例原因不明复发性流产和82例正常对照的亚甲基四氢叶酸还原酶基因C677T和A1298C位点突变。结果:MTHFR 677 3种基因型(CC、CT和TT)在ACL(+)流产组和对照组分布有统计学差异(P=0.045),进一步分析表明,677TT在患者组中表达频率显著增大(P=0.026),T等位基因频率在患者组中也显著增大(P=0.018),MTHFR1298相关3种基因型(AA、AC和CC)和A、C等位基因频率在2组中分布无差异,同时发现8种C677T/A1298C连锁基因型,但都与ACL(+)复发性流产无关。结论:ACL(+)复发性流产与MTHFR C677T突变有关,表明除自身抗体有关的获得性凝血途径以外,遗传性凝血因素在此种类型的流产发生中也起一定的作用。     

思南县女性5,10-亚甲基四氢叶酸还原酶基因多态性调查及其与血清同型半胱氨酸水平相关性的研究

目的:研究叶酸代谢障碍关键酶基因5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C位点基因多态性与血清同型半胱氨酸(HCY)的相关性。方法:随机以贵州省思南县2 188例女性为研究对象,检测其MTHFR C677T、A1298C基因位点多态性,采用统计学方法分析该地区基因的多态性分布特征,并与其他同等级区域人群既有数据比对分析;对其中276例孕期女性,测定血清HCY浓度,分析该指标与遗传因素的相关性。结果:本县的汉族、苗族、土家族女性MTHFR C677T、A1298C位点基因型及等位基因分布情况差异无统计学意义(P0.05)。本地区汉族女性MTHFR 677TT基因型频率(14.9%)显著低于尚志、三河、寿光、张家港等地人群(P0.05),显著高于陵水县人群(P0.05);与郫县人群数据差异无统计学意义(P0.05)。MTHFR 1298CC基因型频率(4.2%)与郫县人群无统计学差异(P0.05),与其他各地区人群均有统计学差异(P0.05)。血清HCY水平在C677T位点3种基因型间有统计学差异(P0.05),而A1298C位点3种基因型间无统计学差异(P0.05)。结论:本县汉族女性MTHFR基因C677T、A1298C位点多态性分布特征有其自身的特点;C677T位点的多态性变化对血清HCY水平有显著影响。     

叶酸代谢相关酶MTHFR基因多态性与妊娠早期亚临床甲状腺功能减退的相关性研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与妊娠早期亚临床甲状腺功能减退症(SCH)的相关性。方法选择2017年3月至2020年7月于郑州大学附属郑州中心医院产检的121例妊娠早期(12周内)SCH孕妇及352例甲状腺功能正常的孕妇作为研究对象,分别纳入SCH组及对照组。检测孕妇MTHFR基因C677T位点及A1298C位点多态性。结果 (1) Hardy-Weinberg遗传平衡检验示两组各基因型频率分布符合哈温平衡(P0.05);(2) SCH组孕妇C等位基因频率低于对照组(P 0.05);(3)在隐性模型、显性模型、加性模型下,SCH及对照组孕妇MTHFR基因C677T位点基因型比较差异均有统计学意义(P 0.05);(4) MTHFR基因C677T位点TT型患者TSH显著高于CC型、CT型(P 0.05);(5) Logistic多因素分析示,MTHFR基因C677T位点基因型为SCH发生的独立影响因素(P 0.05)。结论 MTHFR基因C677T位点多态性与妊娠早期SCH的发生相关。     

柳州市壮族与汉族女性5,10-亚甲基四氢叶酸还原酶、甲硫氨酸合成酶还原酶基因型和等位基因频率的分布

目的:调查柳州市壮族与汉族女性中5,10-亚甲基四氢叶酸还原酶(MTHFR)及甲硫氨酸合成酶还原酶(MTRR)基因的单核苷酸多态性分布特征。方法:通过横断面调查研究方法,以广西省柳州市372位壮族和478位汉族女性为研究对象,检测其MTHFR C677T、A1298C和MTRR A66G基因位点多态性,统计分析该地区基因多态性的分布特征,并与已报道的其他地区少数民族女性数据进行比较。结果:该地区壮族和汉族女性比较,MTHFR C677T的基因型频率差异在两者间有统计学意义(P0.05),而MTHFR A1298C和MTRR A66G两者间无统计学差异(P0.05);MTHFR C677T和A1298C的等位基因频率在两民族间的差异有统计学意义(P0.05),而MTRR A66G则无统计学差异(P0.05)。该地区壮族女性MTHFR C677T的基因型频率和等位基因分布与延边朝鲜族、新疆维吾尔族、银川回族、思南苗族、思南土家族、柳州苗族、三亚黎族间差异均有统计学意义(P0.05);而该地区壮族女性MTHFR A1298C的基因型频率和等位基因分布与延边朝鲜族、银川回族、思南苗族、思南土家族间亦有统计学差异(P0.05);MTRR A66G的分布上则与新疆维吾尔族、思南苗族、思南土家族、南宁壮族、三亚黎族有统计学差异(P0.05)。结论:广西省柳州市壮族女性的MTHFR和MTRR基因多态性分布特征与该地区汉族女性不同,与其他地区少数民族也不相同。     

广东籍汉族妇女N5,10-MTHFR基因和eNOS基因多态性与子痫前期和子痫相关性的研究

目的:探讨N5,10-亚甲基四氢叶酸还原酶(MTHFR)基因及内皮型一氧化氮合酶(eNOS)基因多态性与广东籍汉族妇女子痫前期和子痫发病的关系。方法:567例广东籍汉族妇女中54例诊断为子痫前期或子痫,513例为正常妊娠(对照组)。应用PCR-RFLP方法,检测567例早孕期妇女外周血MTHFR基因C677T突变和eNOS基因G894T突变,计算各基因型的相对风险率。结果:子痫前期和子痫组MTHFR C/C、C/T及T/T基因型频率分别为59.2%、20.4%及20.4%,其中T/T基因型频率显著高于对照组(5.5%)(P<0.001),并且T等位基因频率为30.6%,显著高于对照组(20.5%)(P<0.05),T/T基因型在子痫前期或子痫发病中的相对风险率为4.431。子痫前期和子痫组的eNOS基因频率与对照组无显著差异。结论:广东籍汉族妇女MTHFR基因C677T多态性可能与子痫前期或子痫发病的易感性相关,eNOS基因G894T多态性与子痫前期或子痫发病的易感性无关。     

MTHFR基因多态性与不明原因习惯性流产的相关性分析

目的:观察亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多态性是否为不明原因习惯性流产(RSA)的危险因素。方法:选择早期妊娠93例,其中有RSA史36例,正常早期妊娠对照组57例,采用聚合酶链反应-限制性片段长度多态性技术,检测MTHFR基因C677T多态性。结果:Logistic回归分析显示MTHFR基因多态性是RSA发病的危险因素,RSA组MTHFR基因C677T突变TT型的频率为55.6%(20/36),明显高于对照组31.6%(18/57),P=0.022(OR值2.7,95%CI:1.1~6.4)。RSA组T等位基因频率显著高于对照组(P=0.022)。结论:MTHFR基因型是RSA的危险因素之一。     

叶酸代谢相关基因的多态性与唐氏综合征的关系

目的 研究叶酸代谢中亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因的的遗传多态性是否与唐氏综合征(down syndrome,DS)的发生相关. 方法选择100例生育过DS患儿的汉族母亲为研究组和100例相匹配的汉族母亲为对照组,使用PCR-RFLP和MGB-Taqman实时PCR方法检测MTHFR 677和MTHFR 1298的基因型,化学发光法检测血浆同型半胱氨酸(homocysteine,HCY)的水平. 结果 MTHFR 677和MTHFR 1298一个和/或两个等位基因的变异可使生育DS患儿的风险率分别增加2.37倍(95%CI:1.32～4.27)和1.97倍(95%CI:1.04～3.75).同时合并MTHFR 677CT和1298AC/CC可使DS的发病风险率显著增高,OR=5.62(95%CI:1.86～17.03),而MTHFR 677TT合并1298AC/CC的基因型组合使OR=11.84(95%CI:1.39～100.62).研究组血浆HCY水平显著高于对照组[(9.04±3.85)μmol/L和(6.53±2.06)μmol/L,P<0.01].MTHFR 677一个和/或两个等位基因C→T的变异,使研究组和对照组HCY水平均显著增加(P<0.05).单纯存在MTHFR 1298A/C时两组血浆HCY水平无统计学差异(P>0.05).同时存在MTHFR 677CT/TT和1298AC/CC基因组合可使血浆HCY水平增高(P<0.05).结论 HCY/叶酸代谢相关基因的多态与汉族妇女生育DS患儿的风险相关,且可能存在基因的协同作用.     

亚甲基四氢叶酸还原酶基因C677T多态性与男性不育的相关性

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与中国东北人群男性不育的关系。方法:应用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法检测53例健康可育男性和182例不育男性的MTHFR基因C677T位点多态性。结果:弱精子症不育组(AS组)和不明原因不育组(UR组,精液常规正常)的3种基因型和T等位基因频率分别与对照组相比,差异均具有统计学意义(P<0.05)。结论:MTHFR基因C677T多态性可能与中国东北人群男性不育有相关性,且与弱精子症和不明原因不育的发生密切相关。     

不良孕产史人群中血栓前状态易感基因分布调查CSCD

目的 探究血栓前状态易感基因多态性在不良孕产史人群中的分布。方法 收集2018年12月至2021年6月在山西省太原市妇幼就诊的410例有不良孕产史的女性(病例组)和111例无不良孕产史备孕女性(对照组)作为研究对象。采集两组人群EDTA抗凝全血,提取其基因组DNA,利用荧光定量PCR技术检测血栓前状态易感基因多态性在两组人群中的分布。结果 (1) MTHFR A1298 C、PAI-1 5G/4G、FⅤA1691G、FⅡG20210A基因多态性在对照组和病例组中分布差异无统计学意义(P> 0.05);(2) MTRR A66G位点AA、AG、GG基因型在对照组和病例组中分布差异有统计学意义(P <0.05);(3) MTHFR C677T位点AA、AG、GG基因型及G、A等位基因频率在对照组和病例组中的分布差异有统计学意义(P <0.05)。结论 血栓前状态易感基因MTRR A66G位点、MTHFRC677T位点多态性与不良孕产史密切相关。     

Methylenetetrahydrofolate reductase gene polymorphisms in black South Africans and the association with preeclampsia

BACKGROUND: A methylenetetrahydrofolate reductase (MTHFR) polymorphism (1317T --> C) that occurs commonly in black African individuals prompted this study to establish whether this polymorphism, alone or in association with other MTHFR variants, is associated with preeclampsia in black South African women. METHODS: A group of 204 black women with preeclampsia was examined for the 677C --> T, 1298A --> C and 1317T --> C MTHFR polymorphic alleles using standard techniques. Also examined were women with early-onset preeclampsia (n = 67) and gestational hypertension (n = 78). Results were compared with 338 ethnically matched normotensive pregnant women who had normal full-term gestations. RESULTS: No differences in the 677T --> C or 1298A --> C MTHFR alleles were found between the study groups and controls; very few women were homozygous for either variant allele. Significant differences were observed for the 1317T --> C polymorphism: only 39% of preeclamptics were homozygous for the T allele compared with 52% of the control group [p = 0.002; 0.59 (0.42-0.83)]. Heterozygotes occurred significantly more frequently in preeclamptics (51%), compared with controls (41%) [p = 0.019; 1.49 (1.07-2.08)]. Allele frequencies also differed significantly between preeclamptics and controls [p = 0.003; 0.69 (0.53-0.88)]. Allele frequencies in women with gestational hypertension were statistically indistinguishable from those in controls. CONCLUSION: The low frequencies of the 677C --> T and 1298A --> C MTHFR variant alleles in black South Africans imply little or no role for these mutations in preeclampsia in this population group. However, significant differences in the 1317T --> C allele in preeclamptics suggest that the MTHFR gene, or a closely associated gene, may still have some role, as yet undefined, in the pathogenesis of preeclampsia.     

亚甲基四氢叶酸还原酶基因677位多态性、高同型半胱氨酸血症与复发性流产

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)多态性(C677T)与高同型半胱氨酸(Hcy)血症以及复发性流产之间的关系。方法:采用前瞻性病例对照研究方法,收集71例复发性自然流产患者为病例组,另征集同期58例有正常妊娠史者为对照组,利用PCR-RFLP方法研究MTHFR基因多态性(C677T);同时应用酶法测定血清同型半胱氨酸水平;并随访病例组的妊娠结局。结果:①MTHFR基因677位点的3种基因型在病例组和对照组分布分别为CC:14.1%vs 43.1%、CT:49.3%vs 25.9%、TT:36.6%vs 31.0%,组间比较有极显著统计学差异(χ2=14.7,df=2,P=0.001);其中CC基因型在病例组显著降低(P=0.000,OR=0.216,95%CI:0.093-0.505);T等位基因分布在病例组显著升高(61.3%vs 38.7%,P=0.006)。②129例研究对象中TT基因型血同型半胱氨酸水平显著升高(P=0.000):TT为19.0±9.5 nmol/L、CC为13.1±6.2 nmol/L、CT为11.7±4.0 nmol/L,病例组和对照组高Hcy水平组间无统计学差异(P>0.05)。③病例组中有38.0%(27/71)为高Hcy血症,叶酸治疗有效。结论:MTHFR基因多态性(C677T)与复发性流产有关;MTHFR基因TT型与高Hcy血症有关;叶酸可用于治疗高Hcy血症且有助于改善下次妊娠结局。     

Polymorphisms in folate-related enzyme genes in idiopathic infertile Brazilian men

The aim of the study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) polymorphisms in idiopathic infertile Brazilian men and fertile men. Case-control study comprising 133 idiopathic infertile Brazilian men with nonobstructive azoospermia ([NOA] n = 55) or severe oligozoospermia ([SO] n = 78) and 173 fertile men as controls. MTHFR C677T, A1298C, and G1793A; MTRR A66G; and MTR A2756G polymorphisms were studied by quantitative polymerase chain reaction (qPCR). The results were analyzed statistically and a P value <.05 was considered significant. Single-marker analysis revealed a significant association among MTHFR C677T polymorphism and both NOA group (P = .018) and SO group (P < .001). Considering the MTHFR A1298C, MTHFR G1793A, and MTRR A66G polymorphisms, no difference was found between NOA group and SO group. Regarding the MTR A2756G polymorphism, a significant difference was found between NOA and controls, P = .017. However, statistical analysis revealed no association between SO group and controls. Combined genotypes of 3 MTHFR polymorphisms did not identify a haplotype associated with idiopathic infertility. The combinatory analysis of the 3 polymorphisms MTHFR, MTRR, and MTR did not show difference between cases and controls. The findings suggest the MTHFR C677T and MTR A2756G polymorphisms could be an important genetic factor predisposing to idiopathic infertility in Brazilian men.     

不良孕产史人群中血栓前状态易感基因分布调查

Objective?To explore the distribution of prethrombotic state susceptibility gene polymorphisms in the population with a history of poor pregnancy. Methods?From December 2018 to June 2021, 410 women with a history of poor pregnancy and childbirth (research group) and 111 normal women (control group) were collected as the research subjects. EDTA anticoagulated whole blood of the two groups were collected,its genomic DNA were extracted,fluorescence quantitative PCR technology was used to detect the distribution of prethrombotic state susceptibility gene polymorphisms. Results?① There was no significantly difference in MTHFR A1298 C, PAI-1 5G/4G, FⅤ A1691G, FⅡG20210A gene polymorphisms between the two group (P>0.05);② There were significantly difference in the distribution of genotypes in MTRR A66G sites AA,AG,GG between the two group (P<0.05).③ There were significantly difference in the AA,AG,GG genotypes and the G, A allele frequencies at the C677T site of MTHFR between the two group (P<0.05). Conclusion?The prethrombotic state susceptibility gene MTRR A66G locus and MTHFR C677T locus polymorphisms are related to the history of adverse pregnancy and childbirth.     

The effect of single nucleotide genetic polymorphisms of folic acid cycle on the female reproductive system disorders

Abstract

Currently the significant part of reproductive disorders such as refractory pregnancy loss (RPL), infertility, unsuccessful in vitro fertilization (IVF) are thought to be connected with different genetic factors. One of the main hereditary risk factors for obstetrical pathology development is the presence of polymorph alleles in several genes of folic acid cycle. The present study is dedicated to investigation of the effect of folic acid cycle polymorph variants MTHFR C677?T, MTR A2756G and MTRR A66G on the RPL development and unsuccessful IVF. The samples of peripheral blood of 138 women were tested and showed a statistically significant increase of pathologic genetic alleles of MTRR A66G and MTHFR C677T frequency in two groups of patients with reproductive disorders, i.e. RPL and IVF, versus the control group. Also the advantage of simultaneous analysis of three folic cycle genetic polymorphisms at once in women with reproductive function disorder was demonstrated in comparison with the analysis of isolated polymorphism MTHFR C677T. The combination of polymorph alleles has a significant influence on the pathology development and by many times increases the risk of RPL development and unsuccessful IVF.     

Plasminogen activator inhibitor type 1 activity in women with unexplained very early recurrent pregnancy loss

The aim of the study was to assess the independent role of polymorphism 4G/5G (PL 4G/5G)--genotype 4G/4G in plasminogen activator inhibitor type 1 (PAI-1) in the development of very early recurrent pregnancy loss (RPL)--before 10 weeks of gestation of pregnancy. The polymorphism 4G/5G as well as Factor V Leiden (FVL), prothrombin (FII) gene mutation 20210 G > A and polymorphism 677 C > T in methylentetrahydrofolat reductase (MTHFR) gene was investigated in 110 women with recurrent pregnancy loss before 10 weeks of gestation and in 97 healthy women with at least one uncomplicated full-term pregnancy. A significant prevalence of PL 4G/5G in women with RPL was found in comparison to prevalence of the polymorphism in controls (41.8% versus 26.8% respectively in patients and controls, OR: 1.96, 95% CI: 1.05 3.69, p = 0.034). The difference in prevalence of the polymorphism remains still significant after exclusion of patients and control carriers of FVL, FII 202010 G > A and 677 C > T in MTHFR (the prevalence of PL 4G/5G alone was 44.1% and 24% respectively in patients and controls, OR: 2,5, 95% CI: 1,15 5, 45, p = 0.018). The found association of PL 4G/5G in PAI-1 with early recurrent pregnancy loss encourage an extension of the list of inherited thrombophilic factors with this one. This result also could have had an implication for adjustment of further prophylactic low-molecular weight heparin implication in further pregnancy to prevent a poor foetal outcome.     

亚甲基四氢叶酸还原酶基因多态性与不明原因的重复性自然流产的相关性研究

目的 :探讨同型半胱氨酸代谢酶基因亚甲基四氢叶酸还原酶 (MTHFR)基因多态性C6 77T、A12 98C及其联合基因型与不明原因重复性流产 (URSA)的关系。方法 :运用聚合酶链反应 -限制性片段长度多态性技术检测MTHFRC6 77T、A12 98C基因多态性。结果 :①患者组C/C基因型频率显著低于正常对照组者 ,总的突变T等位基因频率显著高于对照组者。MTHFRC6 77T基因型分布与不同年龄、地区、流产时间、流产性质无关 ,与流产次数显著相关。URSA组MTHFRA12 98C三种基因型频率与对照组相比差异无显著性 ,与患者不同临床特征无明显关联。A12 98C杂合子联合C6 77T杂合子基因型发生URSA的危险性无显著增高。结论 :MTHFRC6 77T基因多态性是URSA发病的遗传风险因素 ,而A12 98C基因多态性不是URSA发病的危险因素。     

Methylenetetrahydrofolate reductase polymorphisms are not a risk factor for pre-eclampsia/eclampsia in Australian women

In European and Japanese but not in Australian, American, and South African women, the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism has been reported to be a genetic risk factor pre-eclampsia/eclampsia (PE/E). The recently described A1298C MTHFR gene polymorphism also results in reduced MTHFR enzyme activity, although to a lesser extent than the previously described C677T polymorphism. Heterozygotes for both polymorphisms are reported to have an even lower MTHFR enzymatic activity than seen in homozygotes for the C677T genotype. In this current study we determined the allele frequency of the A1298C MTHFR gene polymorphism in an Australian population and examined this polymorphism alone and in combination with the C677T MTHFR polymorphism for an association with PE/E. Neither the A1298C polymorphism alone nor a combination of both polymorphisms showed an association with PE/E in our population of Australian women.     

Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women

Aim: Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. Material and Methods: Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. Results: The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. Conclusions: The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women.     

Thrombophilic genes alterations as risk factor for recurrent pregnancy loss

Objective: The important polymorphisms leading to inherited thrombophilia are Factor V Leiden (FVL), Prothrombin G20210A and MTHFR C677T and A1298C. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations. Our clinic is one of the referral centers in reproductive biomedicine in which patients in all over Iran refer to; thus the results of this study could be considered clinically beneficial. Besides, in the present study, not only the frequency of specific but also multiple thrombophilic gene alterations were compared in Iranian women with RPL and a control group.

Methods: The patients group comprised 330 women with three or more consecutive RPLs. The control population included 350 women with at least one child and no history of pregnancy loss. FVL, Prothrombin G20210A and MTHFR C677T polymorphisms were analyzed by Strip assay kit. MTHFR A1298C was genotyped by PCR-RFLP.

Results: The frequencies of FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C mutations in patients were 8.48, 4.24, 45.45 and 59.39%, and in controls were 2.86, 2.86, 34.28 and 6%, respectively.

Conclusions: The present data showed that FVL, MTHFR polymorphisms also combined with thrombophilic gene mutations have a strong association with RPL.