Age at menarche (AAM) is an important marker of the pubertal development and function of the hypothalamic–pituitary–ovarian system. It was reported as a possible factor for a risk of uterine leiomyoma (UL). However, while more than 350 loci for AAM have been determined by genome-wide association studies (GWASs) to date, no studies of these loci for their association with UL have been conducted so far. In this study, we analyzed 52 candidate loci for AAM for possible association with UL in a sample of 569 patients and 981 controls. The results of the study suggested that 23 out of the 52 studied polymorphisms had association with UL. Locus rs7759938 LIN28B was individually associated with the disease according to the dominant model. Twenty loci were associated with UL within 11 most significant models of intergenic interactions. Nine loci involved in 16 most significant models of interactions between single-nucleotide polymorphism (SNP), induced abortions, and chronic endometritis were associated with UL. Among the 23 loci associated with UL, 16 manifested association also with either AAM (7 SNPs) or height and/or body mass index (BMI) (13 SNPs). The above 23 SNPs and 514 SNPs linked to them have non-synonymous, regulatory, and expression quantitative trait locus (eQTL) significance for 35 genes, which play roles in the pathways related to development of the female reproductive organs and hormone-mediated signaling [false discovery rate (FDR) ≤ 0.05]. This is the first study reporting associations of candidate genes for AAM with UL.

This study aimed to determine possible association of eight polymorphisms of seven MMP genes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of the MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP12 genes and their gene–gene (epistatic) interactions were analyzed for association with EH in a cohort of 939 patients and 466 controls using logistic regression and assuming additive, recessive, and dominant genetic models. The functional significance of the polymorphisms associated with EH and 114 variants linked to them (r² ≥ 0.8) was analyzed in silico. Allele G of rs11568818 MMP7 was associated with EH according to all three genetic models (OR = 0.58–0.70, p_perm = 0.01–0.03). The above eight SNPs were associated with the disorder within 12 most significant epistatic models (OR = 1.49–1.93, p_perm < 0.02). Loci rs1320632 MMP8 and rs11568818 MMP7 contributed to the largest number of the models (12 and 10, respectively). The EH-associated loci and 114 SNPs linked to them had non-synonymous, regulatory, and eQTL significance for 15 genes, which contributed to the pathways related to metalloendopeptidase activity, collagen degradation, and extracellular matrix disassembly. In summary, eight studied SNPs of MMPs genes were associated with EH in the Caucasian population of Central Russia.

Examine the association of the 4a/4b polymorphism of endothelial nitric oxide synthase (eNOS) with blood pressure in women at late pregnancy. Blood pressure before pregnancy and at the end of gestation (37-40-week term) was measured in 588 women of the Russian ancestry. The women were divided into groups according to the body mass index and the presence of preeclampsia at late pregnancy. The 4a/4b polymorphism of the eNOS gene was genotyped using PCR with subsequent screening of amplified fragment length polymorphisms. The 4a4a eNOS genotype was associated with higher levels of diastolic blood pressure in pregnant women and with more pronounced dynamics of the diastolic and mean arterial pressure in the development of pregnancy (p = 0.02-0.03). Pregnant women with the 4a4a genotype and increased body mass index had higher systolic, diastolic, and mean arterial pressure (p = 0.001-0.009). In pregnant women with preeclampsia, the 4a4a genotype was associated with higher level of diastolic blood pressure at the end of pregnancy (p = 0.04), whereas in the women without preeclampsia this genotype was associated with more pronounced changes of blood pressure at pregnancy (p = 0.02). The results of our study suggest that the genotype 4a4a of the eNOS gene is associated with higher levels of blood pressure in women at the end of pregnancy.