Examine the association of genetic polymorphisms with age at menarche (AAM) in Russian women. Study design: A total of 1613 Russian females were recruited for the study. Fifty two polymorphisms were analyzed for their association with AAM, height, and BMI. The associations were analyzed assuming the additive, dominant, and recessive models and using the loglinear regression as implemented in PLINK v. 2.050. The 2-, 3-, and 4-loci models of gene-gene interactions were analyzed using the MB-MDR method and validated by the permutation test. Main outcome measures: Genetic polymorphism rs6438424 3q13.32 was independently associated with AAM in Russian women. In addition, 14 SNPs were determined as possible contributors to this trait through gene-gene interactions. Results: The obtained results suggest that 14 out of 52 studied polymorphisms may contribute to AAM in Russian women. The rs6438424 3q13.32 polymorphism was associated with AAM according to both additive and dominant models (р perm = 0.005). In total 12 two-, three-, and four-locus models of gene-gene interactions were determined as contributing to AAM (p perm ≤ 0.006). Nine of the 14 AAM-associated SNPs are also associated with height and BMI (p perm ≤ 0.003). Among 14 AAM-associated SNPs (a priori all having regulatory significance), the highest regulatory potential was determined for rs4633 COMT, rs2164808 POMC, rs2252673INSR, rs6438424 3q13.32, and rs10769908 STK33. Eleven loci are cis-eQTL and affect expression of 14 genes in various tissues and organs (FDR < 0.05). The neuropeptide-encoding genes were overrepresented among the AAM-associated genes (p bonf = 0.039). Conclusions: The rs6438424 polymorphism is independently associated with AAM in Russian females in this study. The other 14 SNPs manifest this association through gene-gene interactions. in the later life. Early menarche may increase a risk for obesity (Guo and Ji, 2011), uterine myoma (Wise and Laughlin-Tommaso, 2016), endometriosis (Nnoaham et al., 2012), breast cancer (Yermachenko and Dvornyk, 2014), cardiovascular diseases (Feng et al., 2008), type 2 diabetes mellitus, infertility and psychological problems (Yermachenko and Dvornyk, 2014).
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.
Introduction: Malfunctioning of the cardiovascular system during pregnancy may be responsible for adverse effects on the 'mother-fetus' system. The cardiovascular system of a pregnant woman develops adaptation to the increased load. Angiotensin-converting enzyme (ACE) is known to play an important role in the adaptation. The present study was designed to investigate whether the insertion-deletion (I/D) polymorphism of the ACE gene is associated with the level of arterial blood pressure in women before and during pregnancy. Materials and methods: The level of blood pressure was measured in 591 Russian women (Central Russia) before and during (37-40 weeks term) pregnancy. The women were divided into three groups which were hypertensive, hypotensive, and normotensive according to blood pressure level. Genotyping of the ACE I/D polymorphism was performed using polymerase chain reaction (PCR) and amplified fragment length polymorphism assay. Results: Women with genotype DD showed the highest blood pressure level both during and at the end of pregnancy (p<0.05). The highest frequencies of allele D and genotype DD were found in pregnant women in the hypertensive group. Conclusions: The deletion variant of the ACE gene is associated with high blood pressure level at the end of pregnancy.
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