Filaggrin gene polymorphisms are associated with atopic dermatitis in women but not in men in the Caucasian population of Central Russia

Abstract

Background and purpose This study aimed to analyze the gender-specific association of the filaggrin (FLG) gene polymorphisms with atopic dermatitis (AD) in Caucasians from the central region of Russia. Methods The study sample consisted of 906 female (including 474 patients with AD and 432 controls) and 406 male (such as 226 patients with AD and 180 controls) participants. Genotyping of ten polymorphisms of the FLG gene was done. The logistic regression was used to analyze the associations. A total of 125 SNPs (seven AD-associated SNPs and 118 proxy SNPs, r2≥0.8) FLG gene were used for the in silico functional annotation analysis in the females. Results Significant associations were identified between seven SNPs of the FLG gene (rs12130219, rs61816761, rs558269137, rs12144049, rs3126085, rs471144, rs6661961) and AD in females: rs12144049 was associated independent individually (for allele C OR = 1.71, 95%Сl 1.19–2.46, рperm = 0.004 and OR = 1.76, 95%Сl 1.18–2.63, рperm = 0.006 according to the additive and dominant genetic models, respectively) and seven SNPs of the FLG gene within 14 haplotypes. Haplotype GGT [rs61816761-rs3126085-rs12144049] showed the strongest association (OR = 0.55, рperm = 0.001). No association between the analyzed SNPs and AD was determined in the male group. The subsequent bioinformatic analysis predicted the SNPs of the FLG gene that possessed epigenetic and non-synonymous effects, were involved in the control of gene expression and alternative splicing of genes that contribute to AD pathophysiology. Conclusion Polymorphisms of the FLG gene are associated with AD in females but not in males in the Caucasian population of Central Russia.

Infant lung function and early skin barrier impairment in the development of asthma at age 3 years

“…In line with previous reports, 1 boys more often had lower lung function in infancy and asthma at age 3 years, which partly may explain the observed associations. Dvornyk et al 47 . identified an association between single nucleotide polymorphisms in FLG and AD in Caucasian women, but not in men.…”

“…Based on the literature, sex, 35,36 GA, 35,37 tobacco smoke exposure in pregnancy, 38 urban living environment in pregnancy, 39,40 breastfeeding, 41,42 parental atopy, 43 parental education level, 44,45 study center, 46 and the PreventADALL interventions were treated as possible confounders. Models including FLG mutations were adjusted for sex 16,47 . Results are presented as odds ratio (OR) and adjusted OR (aOR) with 95% CI.…”

“…Models including FLG mutations were adjusted for sex. 16,47 Results are presented as odds ratio (OR) and adjusted OR (aOR) with 95% CI. Analyses for possible interactions between t PTEF /t E , t PTEF , TEWL, eczema and FLG mutations, the PreventADALL interventions and asthma at age 3 years were conducted.…”

“…In line with previous reports, 1 boys more often had lower lung function in infancy and asthma at age 3 years, which partly may explain the observed associations. Dvornyk et al 47 identified an association between single nucleotide polymorphisms in FLG and AD in Caucasian women, but not in men. In conflict with an Australian publication (n = 620) reporting infantile eczema being associated with asthma in boys, 56 the presence of eczema, regardless of an AD diagnosis, was not associated with asthma at age 3 years.…”

Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia

“…To estimate the potential downstream functional effects of the POAG-associated variants and their proxies, 44,45 we used the available data on epigenetic effects (HaploReg, 29 ) non-synonymous functional predictions (SIFT 46 and PolyPhen-2 47 databases), expression (eQTL) (Blood eQTL browser 48 and Genotype-Tissue Expression (GTE) × Consortium atlas 49 ) and alternative splicing (sQTL) quantitative traits (GTEx Consortium atlas. 49 ) HaploReg was used to identify variants in strong linkage disequilibrium (LD, r 2 ≥ 0.80) 50 with the POAG-associated variants.…”