Association of genetic polymorphisms with age at menarche in Russian women

Abstract

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).

Dataset of allele and genotype frequencies of the three functionally significant polymorphisms of the MMP genes in Russian patients with primary open-angle glaucoma, essential hypertension and peptic ulcer

“…Three SNPs of the MMP genes (rs1799750 MMP1 , rs3918242 and rs17576 MMP9 ) were selected for the analysis. The following selection criteria were applied [ 48 , 49 ]: 1) Previously reported associations with POAG, EH and PU ( Table 2 ), 2) Regulatory potential (regSNP) ( Table 3 ), 3) Effect on gene expression (eSNP) ( Table 4 ), 4) Splicing QTLs (sSNP) ( Table 5 ), and 5) MAF > 5%.…”

Using the method of Multifactor Dimensionality Reduction (MDR) and its modifications for analysis of gene-gene and gene-environment interactions in genetic-epidemiological studies (review)

“…В качестве примера эффективности использования метода MDR и его модификации MB-MDR для оценки ген-генных взаимодействий, ассоциированных с формированием количественных мультифакториальных признаков, приведем полученные нами результаты генетико-эпидемиологического исследования возраста менархе, опубликованные в журналах GENE [40]. Нами с помощью метода MB-MDR изучены ассоциации ген-генных взаимодействий 52 SNPs с возрастом менархе у женщин России.…”

“…При обозначении полиморфизма указаны хромосома и rs SNP. Цвет линии отражает характер взаимодействия между полиморфизмами: красный и оранжевый указывает на выраженный и умеренный синергизм, коричневый -независимый эффект отдельных локусов, зеленый и синий -умеренный и выраженный антагонизм соответственно [40]. Fig.…”

“…When referring to a polymorphism, the chromosome and rs SNP are indicated. The color of the line reflects the nature of the interaction between polymorphisms: red and orange indicates pronounced and moderate synergism, brown indicates the independent effect of individual loci, green and blue indicates moderate and pronounced antagonism, respectively [40]. В отношении данной статьи не было зарегистрировано конфликта интересов.…”

The contribution of gene-gene interactions of polymorphic loci of matrix metalloproteinases to susceptibility to primary open-angle glaucoma in men

“…Для молекулярно-генетического исследования были отобраны 8 полиморфных локусов генов матриксных металлопротеиназ rs3918249, rs3787268, rs2250889, rs17577, rs17576, rs3918242 гена ММР-9, rs1799750 гена ММР-1, rs679620 гена ММР-3 с учетом их значимого влияния на экспрессию и регуляторный потенциал генов [26].…”