Polymorphisms of genes involved in inflammation and blood vessel development influence the risk of varicose veins |
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| Authors: | A. Shadrina Y. Tsepilov M. Smetanina E. Voronina E. Seliverstov E. Ilyukhin A. Kirienko I. Zolotukhin M. Filipenko |
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| Affiliation: | 1. Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Theoretical and Applied Functional Genomics Laboratory, Novosibirsk State University, Novosibirsk, Russia;2. Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Theoretical and Applied Functional Genomics Laboratory, Novosibirsk State University, Novosibirsk, Russia;3. Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk, Russia;4. Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Department of Natural Sciences, Novosibirsk State University, Moscow, Russia;5. Department of Faculty Surgery, Pirogov Russian National Research Medical University, Moscow, Russia;6. Private Surgery Center “Medalp”, Saint Petersburg, Russia;7. Department of Faculty Surgery, Pirogov Russian National Research Medical University, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia |
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| Abstract: | Heredity plays an important role in the etiology of varicose veins (VVs). However, the genetic basis underlying this condition remains poorly understood. Our aim was to replicate top association signals from genome‐wide association studies (GWASs) for VVs of lower extremities using 2 independent datasets—our sample of ethnic Russian individuals (709 cases and 278 controls) and a large cohort of British residents from UK Biobank (10 861 cases and 397 594 controls). Associations of polymorphisms rs11121615, rs6712038, rs507666, rs966562, rs7111987, rs6062618, and rs6905288 were validated in the UK Biobank individuals at a Bonferroni‐corrected significance level. In Russian cohort, only rs11121615 reached a nominal significance level of P < .05. Results of original GWAS and replication studies were combined by a meta‐analysis, and polymorphisms listed above as well as rs111434909 and rs4463578 passed a genome‐wide significant threshold. Notably, the majority of these polymorphisms were located within or near genes involved in vascular development and remodeling, and regulation of inflammatory response. Our results confirm the role of these polymorphisms in genetic susceptibility to VVs and indicate the revealed genomic regions as good candidates for further fine‐mapping studies and functional analysis. Moreover, our findings implicate inflammation and abnormal vascular architecture in VVs pathogenesis. |
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| Keywords: | genetic polymorphism genome‐wide association study meta‐analysis varicose veins |
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