Balkan Journal of Medical Genetics

INHERITED THROMBOPHILIAS COULD INFLUENCE THE REPRODUCTIVE OUTCOME IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS
robeva r1,*, Tanev D2, andonova S3, Nikolova M4, Tomova a1, Kumanov Ph1, Savov a3, Rashkov R2, Kolarov Zl2,*
*Corresponding Author: Professor Zlatimir Kolarov, M.D., Ph.D., D.MSc., Clinic of Rheumatology, Medical University Sofia, 13 Urvich Str., Sofia 1612, Bulgaria. Tel: +359-2-958-93-91. Fax. +359-2-958-23-31. E-mail: zkolarov@abv.bg and Ralitsa Robeva, M.D., Ph.D., Clinical Center of Endocrinology and Gerontology, Medical University Sofia, 2 Zdrave Str., Sofia 1431, Bulgaria. Tel: +359-2-895-60-40. Fax: +359-2-987-41-45. E-mail: rali_robeva@yahoo.com
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DISCUSSION

Factor V Leiden and FIIg20210a are the most frequently investigated genetic polymorphisms related to hypercoagulability, venous thromboembolism and recurrent pregnancy loss [16,17]. Both polymorphisms were thoroughly investigated in SLE patients, but the studies were focused primarily on disease-related thrombotic events [9,11]. The largest study that investigated risk factors for thrombosis in SLE patients suggested that the genetic predisposition for obstetric and non-obstetric thrombosis in lupus patients might be similar [11]. Accordingly, the present study aimed to investigate the influence of inherited thrombophilias on some reproductive aspects of SLE women. The results showed that the FVleiden allele carriers reported a lower number of pregnancies and live births irrespective of the presence of the saPS. as the self-reported prevalence of menstrual irregularities was similar in both groups, an increased frequency of unrecognized chemical pregnancy loss is one of the possible hypotheses. Factor V Leiden was already associated with a higher rate of preclinical pregnancy losses and very early recurrent miscarriages in otherwise healthy women [18,19]. The mutant allele was not associated with fetal losses in the investigated SLE patients, although in healthy women FVleiden increased the risk for second trimester miscarriages and stillbirths due to uteroplacental insufficiency [19-21]. As FVleiden and lupus are both independently related to a resistance against ac tivated protein C and hypercoagulability, their synergistic effect could lead to an earlier miscarriage than in women without the autoimmune disease [22]. Ineffective blood flow caused by a vascular insufficiency in the trophoblast might impair the developing pregnancy in mothers with several prothrombotic risk factors [18]. Contrary to our results, Regéczy et al. [8] found significantly higher prevalence of fetal losses in FVleiden carriers than in other SlE women. The discrepancies could be explained by the low number of mutation carriers, different characteristics of SLE patient groups and ethnic peculiarity, but nevertheless, both studies showed that FVleiden could be an important genetic factor in the deteriorating reproductive outcomes in lupus patients. The prevalence of the g20210a polymorphism in the prothrombin gene did not increase the risk for SLE development and did not influence the thrombotic risk in patients with lupus [9,11,23]. FIIg20210a was related to increased prevalence of recurrent miscarriages in the general population [17], but data concerning SLE patients were scarce. The present study did not find any significant associations between the mutant allele and the reproductive outcomes in SLE patients. However, no definitive conclusions could be drawn, because of the small number of FIIg20210a carriers. The MTHFRC677T polymorphism was widely investigated in different thrombotic and cancer diseases, and ethnic-dependent associations were found [24,25]. The prevalence of the MTHFRC677T polymorphism was also investigated in SLE patients [26,27]. Afeltra et al. [26] found an increased frequency of TT but not CT genotypes in lupus patients compared to controls, while Summers et al. [27] did not find any differences. Our data did not show significant differences between patients and controls, although the prevalence of heterozygous CT carriers in SLE patients was increased. Further larger studies are needed to establish the possible influence of the MTHFRC677T polymorphism on SlE development. According to our results the MTHFRC677T TT genotype increased the risk of at least one miscarriage in lupus women. MTHFRC677T was significantly associated with recurrent miscarriages in Asian women, while the results in Caucasians were conflicting [28-30]. After adjustment for sAPS, the association between MTHFRC677T polymorphism and spontaneous abortion was attenuated, thus, synergistic effects of the immunological and genetic factors in SLE could not be excluded. The main limitations of the study were the small number of pregnancies in the group of SLE patients as well as the self-reported reproductive history without data from medical records where other confounding factors could be included. Nevertheless, the present data showed that inherited thrombophilias could influence the reproductive outcome in women with SLE. Interestingly, the same polymorphisms modulate the thrombosis risk in EuropeanAmerican SLE patients [11]. Thus, further studies in other ethnic groups would be of strong clinical importance.

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