Differentially Expressed Genes in Varicose Veins Disease: Current State of the Problem, Analysis of the Published Data

Abstract

1. Патогенез ВБНК и проблемы его изучения Варикозная болезнь нижних конечностей (ВБНК)-широко распространенная патология сосудов, встречающаяся в среднем у 25-50% женщин и 10-30% мужчин [1-3]. Оценки распространенности заболевания варьируют от исследования к исследованию, что, по всей видимости, связано с осо-бенностями изучаемых выборок, в первую очередь с разным влиянием факторов риска, главными из которых являются женский пол, возраст, семейный анамнез заболевания, беременность, а также ожире

The genetic constituent of varicose vein pathogenesis as a key for future treatment option development

“…Recently, two fairly large bioinformatics (non-experimental) works using modern approaches to big data analysis were published almost in parallel by American and Swedish scientists in 2018 in Circulation [26] and Russian scientists in 2019 in PLoS Genetics [27] . After analyzing data from the UK Biobank, the authors of these papers presented a comprehensive genetic and epidemiological study on VVs and identified new clinical and genetic risk factors.…”

“…They denoted the genes in closest proximity to the variants (and not only those genes): CASZ1, LBH, PPP3R1, IGSF11, GATA2-AS1, STIM2, TEMN3-AS1, AGGF1, EBF1, SLC12A2, HISTIH3G, HCG9, HLA-B, LINC02549, RSPO3, ALDH8A1, PRKAR1B, CNGB3, DEC1, HDAC7, DAOA, LINC00924, GLG1, CTU2, PIEZO1, KCNJ2, LINC01152, MAMSTR, NFATC2,ZNF512B [26] . Shadrina et al [27] used genetic association data on VVs for 337,199 individuals (6958 cases and 330,241 controls) and demonstrated direct causal effects of the anthropometric traits, such as height and weight (and not only those traits), as well as plasma levels of immune-related proteins MICB and CD209. Their large-scale GWA identified 12 reliably associated loci that explain 13% of the SNP-based heritability of VVs, prioritizing the most likely causal genes (shown in brackets): rs11121615 (CASZ1), rs2911463 (PIEZO1, CTU2), rs2861819 (PPP3R1, PNO1), rs3101725 (SLC12A2, FBN2, LINC01184), rs11135046 (EBF1), rs28558138 (STIM2), rs7773004 (HFE), rs12625547 (NFATC2), rs2241173 [SOX9, AC005152.3 (LOC102723505)], rs73107980 [COL2A1, RAPGEF3 (EPAC1)], rs9880192 (GATA2) and rs236530 (KCNJ16, KCNJ2) [27] .…”

“…Shadrina et al [27] used genetic association data on VVs for 337,199 individuals (6958 cases and 330,241 controls) and demonstrated direct causal effects of the anthropometric traits, such as height and weight (and not only those traits), as well as plasma levels of immune-related proteins MICB and CD209. Their large-scale GWA identified 12 reliably associated loci that explain 13% of the SNP-based heritability of VVs, prioritizing the most likely causal genes (shown in brackets): rs11121615 (CASZ1), rs2911463 (PIEZO1, CTU2), rs2861819 (PPP3R1, PNO1), rs3101725 (SLC12A2, FBN2, LINC01184), rs11135046 (EBF1), rs28558138 (STIM2), rs7773004 (HFE), rs12625547 (NFATC2), rs2241173 [SOX9, AC005152.3 (LOC102723505)], rs73107980 [COL2A1, RAPGEF3 (EPAC1)], rs9880192 (GATA2) and rs236530 (KCNJ16, KCNJ2) [27] . All of those SNPs are the same as those found by Fukaya et al [26] , and only the last two are not in the top 30.…”