Association of Plasminogen Activator Inhibitor-1 Gene Polymorphisms and Methylene Tetrahydrofolate Reductase Polymorphisms with Spontaneous Miscarriages

Abstract

Aim: The objective of this study was to investigate a possible correlation between the plasminogen activator inhibitor-1 (PAI-1) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and unexplained spontaneous miscarriages (SM). Materials and Methods: PAI-1 polymorphisms were evaluated in 150 women with pregnancy in their history. One hundred women with a history of SM formed the study group and 50 women with normal pregnancies served as the control group. Also, the combination of PAI-1 and MTHFR polymorphisms were evaluated in 138 women out of a total of 150, which included 92 women with SM in their history compared to 46 women in the control group. For statistical analysis, χ² test, Phi, and Cramer V tests were used; p < 0.05 was taken as a statistically significant result. Results: Our findings show: (a) the correlation between SM and PAI-1 mutations reaches statistical significance (p = 0.026); (b) there was a statistically significant difference between heterozygous PAI-1 in women with only 1 SM compared to the control group (p = 0.047); (c) the comparison of combinations of both mutations, PAI-1 and MTHFR, with the control group demonstrates statistical significance in favor of women with SM and both mutations (p = 0.022). Conclusion: PAI-1 and MTHFR polymorphisms may play an important role in pregnancy complications because heterozygous PAI-1 mutations and a combination of both PAI-1 and MTHFR mutations might contribute to SM.

The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review

“…Twenty-one studies investigated cases with preeclampsia, 22 24 34 35 36 45 47 49 54 61 67 69 70 71 72 73 74 75 86 87 92 45 studies investigated cases with pregnancy loss described as pregnancy loss, 27 29 31 39 50 51 52 59 60 64 66 68 81 90 91 miscarriage, 23 28 30 38 40 41 42 44 53 55 56 57 58 62 65 76 78 79 88 abortion, 37 43 48 63 77 83 89 fetal loss, 46 80 82 or intrauterine fetal death. 84 One study investigated cases delivering still birth, 33 one study investigated cases delivering newborns meeting the criteria for intrauterine growth restrictions, 26 and three studies investigated cases with various adverse pregnancy outcomes.…”

“…Four studies (9%) investigated only miscarriage in 1 st trimester, 23 58 59 68 11 studies (24%) investigated miscarriage until 20 weeks of gestational age (GA), 27 42 50 51 53 56 62 64 65 76 89 three (7%) until 22 GA, 40 41 57 one (2%) until 23 GA, 28 and three (7%) until 25 GA. 37 38 44 Three studies (7%) investigated women with both early and late losses, 31 39 60 and finally 20 studies (44%) did not define any criterion for when the pregnancy loss occurred. 29 30 43 46 48 52 55 63 66 77 78 79 80 81 82 83 84 88 90 91 Ten studies (22%) included only cases with three or more pregnancy losses, 23 28 29 30 37 38 42 50 52 58 26 studies (58%) included cases with two or more pregnancy losses, 27 31 39 40 41 44 48 51 53 55 56 57 59 60…”

“…In 44 out of 45 studies the -675 4G/5G polymorphism was examined. Among these, 23 studies (52%) found no significant associations between 4G/5G polymorphism and pregnancy loss reported as either no difference in the genotype distribution comparing cases and controls 23 31 38 40 42 43 44 46 52 56 57 58 65 77 81 83 84 88 and/or no significantly increased odds of pregnancy loss comparing either 4G/4G genotype to 4G/5G + 5G/5G (the recessive model), 28 30 52 57 80 4G/4G + 4G/5G to 5G/5G genotype (the dominant model) 42 51 53 58 88 or 4G/4G to 5G/5G. 23…”

“…Table 2 shows extracted data from the 11 studies investigating the association between PAI-1 levels in pregnant women and placenta-mediated pregnancy complications. Of the 71 included studies, 15 were rated good, 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 39 were rated fair, 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 and 17 were rated poor. 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92…”

“…In 32 of the 59 studies investigating PAI-1 4G/5G polymorphism and placenta-mediated pregnancy complications no association between PAI-1 4G/5G polymorphism and placenta-mediated pregnancy complications was identified. 22 23 24 26 28 30 31 32 38 40 42 43 44 45 46 49 51 52 53 56 57 58 61 65 77 80 81 83 84 85 87 88…”