The prevalence and linkage disequilibrium of 21 genetic variations related to thrombophilia, folate cycle, and hypertension in reproductive age women of Rostov region (Russia).

Several maternal genetic variations are known to play an important role during pregnancy since they can affect mother health and/or fetal growth. The frequency of these variants is variable among different populations. This study aimed to investigate thrombophilia, folate metabolism and hypertension genetic variants in reproductive age women of Rostov region (Russia) and then assess their linkage disequilibrium (LD) and heterogeneity among populations. A total of 3108 reproductive age women were included (33.75 ± 5.13 years). Twenty-one genetic variants were detected with RT-PCR. LD was tested according to (D') coefficient and p value. The highest frequency of mutant allele in studied population was as follows: PAI-1 rs1799768, MTRR rs1801394, AGT rs699, and AGTR2 rs1403543. We showed a high possibility of coinheritance of MTHFR rs1801133 with rs1801131 and AGT rs699 with rs4762 (D'=0.992 and 0.999, respectively). In addition, comparative analysis showed F7 rs6046, FGB rs1800790, MTR rs1805087, and AGT rs699 significantly more frequent among Rostov females by 1.3-1.5 times than European. MTHFR rs1801133, ADD1 rs4961, AGTR2 rs1403543, NOS3 rs2070744, and rs1799983 were with higher frequencies in Europeans than those in the studied group. Our data could be used as a reference for further associative studies of targeted genetic variations in different pregnancy complications specifically in this population.

The Effect of Estrogen-Related Genetic Variants on the Development of Uterine Leiomyoma: Meta-analysis.

Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age. It has been diagnosed approximately in 5 to 69% of women and was symptomatic in 30% of them. The underlying pathobiology of uterine leiomyoma is not well understood yet, but it can be defined as an estrogen-dependent tumor. Thus, this meta-analysis aimed to investigate ESR1rs9340799 (XbaI, A351G), ESR1rs2234693 (Pvull, T397C), and COMT rs4680 (Val158Met) polymorphisms, which affect estrogen functioning and metabolism, in association with UL risk. According to PRISMA protocol, systematic searching of databases resulted 24 included studies. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were used to evaluate associations of the three targeted polymorphisms with uterine leiomyoma risk in dominant model of inheritance. Meta-analysis included 4969 women diagnosed with uterine leiomyoma and 4934 controls. ESR1 (XbaI, A351G) polymorphism showed no significant association with uterine myeloma risk (OR = 1.19, 95% CI 0.98-1.45, P = 0.07). ESR1 (Pvull, T397C) was associated with a higher risk of uterine leiomyoma, but only in Asian (OR = 1.78, 95% CI 1.30-2.45, P = 0.0004) and COMT (Val158Met) according to our data is significantly associated with a lower risk of leiomyoma (OR = 0.83, 95% CI 0.71-0.97, P = 0.02). Our updated meta-analysis provided statistical evidence for the protective role of COMT (Val158Met) in association with the susceptibility to uterine leiomyoma and the possible role of ESR1 (Pvull, T397C) as a risk factor of this tumor.