TY - JOUR

T1 - Polymorphisms of genes involved in inflammation and blood vessel development influence the risk of varicose veins

AU - Shadrina, A.

AU - Tsepilov, Y.

AU - Smetanina, M.

AU - Voronina, E.

AU - Seliverstov, E.

AU - Ilyukhin, E.

AU - Kirienko, A.

AU - Zolotukhin, I.

AU - Filipenko, M.

N1 - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - genetic polymorphism

KW - genome-wide association study

KW - meta-analysis

KW - varicose veins

UR - http://www.scopus.com/inward/record.url?scp=85049802993&partnerID=8YFLogxK

U2 - 10.1111/cge.13362

DO - 10.1111/cge.13362

M3 - Article

C2 - 29660117

AN - SCOPUS:85049802993

VL - 94

SP - 191

EP - 199

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 2

ER -