Sex Hormone Candidate Gene Polymorphisms Are Associated with Endometriosis

Golovchenko, I.O.; Aizikovich, Boris; Головченко, О. В.; Reshetnikov, Evgeny; Churnosova, Maria; Aristova, Inna; Ponomarenko, Irina; Churnosov, Mikhail

doi:10.3390/ijms232213691

Cited by 13 publications

(6 citation statements)

References 90 publications

(174 reference statements)

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“…For the purpose of biological interpretation of the identified associations (establishing the mechanisms underlying these associations), we used in silico information on the assumed functional ability of HTN-related polymorphisms (taking into account strongly coupled loci with a coupling strength of at least 0.80 [134,135]) and genes. We used such seven bioinformatics databases as (1) HaploReg [116] (determination of the regulatory potential of polymorphisms: location in putative promoters/enhancers, association with transcription factors/regulatory proteins, localization in regions of open chromatin and evolutionarily conservative DNA sites), (2) SIFT [136] and (3) PolyPhen-2 [137] (identification and evaluation of predictive potential of non-synonymous SNPs), (4) GTEx [138] (correlation of loci with gene expression and alternative splicing in 54 different organs/tissues), (5) Blood eQTL browser [139] (the relationship of SNPs with gene expression in peripheral blood), (6) Gene Ontology [140] (identification of HTN-associated genes pathways), (7) Gen-eMANIA [141] (estimation and visualization of the mechanisms of intergenic interactions of HTN-significant genes).…”

Section: Definition Of the Alleged Functional Ability Of Htn-related ...mentioning

confidence: 99%

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia

Иванова

Churnosova

Abramova

et al. 2023

IJMS

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The aim of the study was directed at studying the sex-specific features of the correlation between genome-wide association studies (GWAS)-noticeable polymorphisms and hypertension (HTN). In two groups of European subjects of Russia (n = 1405 in total), such as men (n = 821 in total: n = 564 HTN, n = 257 control) and women (n = 584 in total: n = 375 HTN, n = 209 control), the distribution of ten specially selected polymorphisms (they have confirmed associations of GWAS level with blood pressure (BP) parameters and/or HTN in Europeans) has been considered. The list of studied loci was as follows: (PLCE1) rs932764 A > G, (AC026703.1) rs1173771 G > A, (CERS5) rs7302981 G > A, (HFE) rs1799945 C > G, (OBFC1) rs4387287 C > A, (BAG6) rs805303 G > A, (RGL3) rs167479 T > G, (ARHGAP42) rs633185 C > G, (TBX2) rs8068318 T > C, and (ATP2B1) rs2681472 A > G. The contribution of individual loci and their inter-locus interactions to the HTN susceptibility with bioinformatic interpretation of associative links was evaluated separately in men’s and women’s cohorts. The men–women differences in involvement in the disease of the BP/HTN-associated GWAS SNPs were detected. Among women, the HTN risk has been associated with HFE rs1799945 C > G (genotype GG was risky; ORGG = 11.15 ppermGG = 0.014) and inter-locus interactions of all 10 examined SNPs as part of 26 intergenic interactions models. In men, the polymorphism BAG6 rs805303 G > A (genotype AA was protective; ORAA = 0.30 ppermAA = 0.0008) and inter-SNPs interactions of eight loci in only seven models have been founded as HTN-correlated. HTN-linked loci and strongly linked SNPs were characterized by pronounced polyvector functionality in both men and women, but at the same time, signaling pathways of HTN-linked genes/SNPs in women and men were similar and were represented mainly by immune mechanisms. As a result, the present study has demonstrated a more pronounced contribution of BP/HTN-associated GWAS SNPs to the HTN susceptibility (due to weightier intergenic interactions) in European women than in men.

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Section: Definition Of the Alleged Functional Ability Of Htn-related ...mentioning

confidence: 99%

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia

Иванова

Churnosova

Abramova

et al. 2023

IJMS

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“…FGR-significant locus/gene probable functions. We explored FGR-correlated loci and LD SNPs (r 2 was not less than 0.80 [ 142 , 143 ]) from the standpoint of their possible functionality [ 144 , 145 , 146 ]. For the purpose of in-depth/comprehensive analysis of materials on this issue, based on the positively proven in extensive (including GWAS) genetic research with an in silico approach [ 147 , 148 , 149 , 150 ], six different contemporary bioinformatic programs/resources were utilized, such as (a) GTE Consortium data [ 151 ], (b) HaploReg [ 128 ], (c) GeneOntology knowledge base [ 152 ], (d) STRING [ 153 ], (e) Blood eQTL resource [ 154 ], and (f) SIFT [ 155 ].…”

Section: Methodsmentioning

confidence: 99%

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk

Reshetnikov,

Churnosova,

Reshetnikova

et al. 2024

IJMS

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We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)–control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/рperm = 0.0003; ORadditive = 0.61/рperm = 0.001; ORdominant = 0.56/рperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/рperm = 0.003;ORadditive = 1.45/рperm = 0.002; ORrecessive = 2.41/рperm = 0.0002),GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/рperm = 0.0003; ORdominant = 1.59/рperm = 0.011; ORadditive = 1.56/рperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/рperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (рperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk.

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“…The probable KOA effector SNPs/genes (taking into account proxy SNPs, r 2 ≥ 0.80 [ 60 , 61 ]) have been chosen for their functionality (the in silico approach was applied [ 62 , 63 ] based on online integrated resources of bioinformatics information [ 64 , 65 , 66 ] including the GTEx [ 67 ], PolyPhen2 [ 68 ], HaploReg [ 39 ], Blood eQTL [ 69 ], SIFT [ 70 ], GeneMANIA [ 71 ]).…”

Section: Methodsmentioning

confidence: 99%

Intergenic Interactions of SBNO1, NFAT5 and GLT8D1 Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia

Novakov

Novakova

Churnosova

et al. 2023

Life

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This study was conducted to examine the associations between genome-wide association studies (GWAS)-important single nucleotide polymorphisms (SNPs) and knee osteoarthritis (KOA) among Europeans of Russia. The present replicative study (“patient-control” design has been used) was carried out on 1000 DNA samples from KOA (n = 500) and KOA-free (n = 500) participants. Ten GWAS-important for KOA SNPs of eight candidate genes (LYPLAL1, GNL3, GLT8D1, SBNO1, WWP2, NFAT5, TGFA, GDF5) were studied. To assess the link between SNPs and KOA susceptibility, logistic regression (to establish independent SNP effects) and MB-MDR (to identify SNP–SNP interactions) were used. As a result of this genetic analysis, the associations of individual SNPs with KOA have not been proven. Eight loci out of ten tested SNPs interacted with each other (within twelve genetic models) and determined susceptibility to KOA. The greatest contribution to the disease development were made by three polymorphisms/genes such as rs6976 (C>T) GLT8D1, rs56116847 (G>A) SBNO1, rs6499244 (T>A) NFAT5 (each was included in 2/3 [8 out 12] KOA-responsible genetic interaction models). A two-locus epistatic interaction of rs56116847 (G >A) SBNO1 × rs6499244 (T>A) NFAT5 determined the maximum percentage (0.86%) of KOA entropy. KOA-associated SNPs are regulatory polymorphisms that affect the expression/splicing level, epigenetic modification of 72 genes in KOA-pathogenetically significant organs such as skeletal muscles, tibial arteries/nerves, thyroid, adipose tissue, etc. These putative KOA-effector genes are mainly involved in the organization/activity of the exoribonuclease complex and antigen processing/presentation pathways. In conclusion, KOA susceptibility among Europeans of Russia is mediated by intergenic interactions (but not the main effects) of GWAS-important SNPs.

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Sex Hormone Candidate Gene Polymorphisms Are Associated with Endometriosis

Cited by 13 publications

References 90 publications

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk

Intergenic Interactions of SBNO1, NFAT5 and GLT8D1 Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia

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