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).

No abstract

No abstract

The aim of this case-control replicative study was to investigate the link between GWAS-impact for arterial hypertension (AH) and/or blood pressure (BP) gene polymorphisms and AH risk in Russian subjects (Caucasian population of Central Russia). AH (n = 939) and control (n = 466) cohorts were examined for ten GWAS AH/BP risk loci. The genotypes/alleles of these SNP and their combinations (SNP–SNP interactions) were tested for their association with the AH development using a logistic regression statistical procedure. The genotype GG of the SNP rs1799945 (C/G) HFE was strongly linked with an increased AH risk (ORrecGG = 2.53; 95%CIrecGG1.03–6.23; ppermGG = 0.045). The seven SNPs such as rs1173771 (G/A) AC026703.1, rs1799945 (C/G) HFE, rs805303 (G/A) BAG6, rs932764 (A/G) PLCE1, rs4387287 (C/A) OBFC1, rs7302981 (G/A) CERS5, rs167479 (T/G) RGL3, out of ten regarded loci, were related with AH within eight SNP–SNP interaction models (<0.001 ≤ pperm-interaction ≤ 0.047). Three polymorphisms such as rs8068318 (T/C) TBX2, rs633185 (C/G) ARHGAP42, and rs2681472 (A/G) ATP2B1 were not linked with AH. The pairwise rs805303 (G/A) BAG6–rs7302981 (G/A) CERS5 combination was a priority in determining the susceptibility to AH (included in six out of eight SNP–SNP interaction models [75%] and described 0.82% AH entropy). AH-associated variants are conjecturally functional for 101 genes involved in processes related to the immune system (major histocompatibility complex protein, processing/presentation of antigens, immune system process regulation, etc.). In conclusion, the rs1799945 polymorphism of the HFE gene and intergenic interactions of BAG6, CERS5, AC026703.1, HFE, PLCE1, OBFC1, RGL3 have been linked with AH risky in the Caucasian population of Central Russia.

No abstract