Role of HIF1A, VEGFA and VEGFR2 SNPs in the Susceptibility and Progression of COPD in a Spanish Population

Rebeca Baz-Dávila; Adriana Espinoza-Jiménez; María Del Cristo Rodríguez-Pérez; Javier Zulueta; Nerea Varo; Ángela Montejo; Delia Almeida-González; Armando Aguirre-Jaime; Elizabeth Córdoba-Lanús; Ciro Casanova

doi:10.1371/journal.pone.0154998

Role of HIF1A, VEGFA and VEGFR2 SNPs in the Susceptibility and Progression of COPD in a Spanish Population

PLoS One. 2016 May 10;11(5):e0154998. doi: 10.1371/journal.pone.0154998. eCollection 2016.

Affiliations

¹ Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
² Pulmonary Department, Clínica Universitaria de Navarra, Pamplona, Spain.
³ Biochemical Analysis Department, Clínica Universitaria de Navarra, Pamplona, Spain.
⁴ Pulmonary Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
⁵ Immunology Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.

Abstract

Hypoxia is involved in the development of chronic inflammatory processes. Under hypoxic conditions HIF1A, VEGF and VEGFR2 are expressed and mediate the course of the resultant disease. The aim of the present study was to define the associations between tSNPs in these genes and COPD susceptibility and progression in a Spanish cohort. The T alleles in rs3025020 and rs833070 SNPs (VEGFA gene) were less frequent in the group of COPD cases and were associated with a lower risk of developing the disease (OR = 0.60; 95% CI = 0. 39-0.93; p = 0.023 and OR = 0.60; 95% CI = 0.38-0.96; p = 0.034, respectively) under a dominant model of inheritance. The haplotype in which both SNPs presented the T allele confirmed the association found (OR = 0.02; 95% CI = 0.00 to 0.66; p = 0.03). Moreover, patients with COPD carrying the T allele in homozygosis in rs3025020 SNP showed higher lung function values and this association remained constant during 3 years of follow-up. In conclusion, T allele in rs833070 and rs3025020 may confer a protective effect to COPD susceptibility in a Spanish population and the association of the SNP rs3025020 with lung function may be suggesting a role for VEGF in the progression of the disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Alleles
Case-Control Studies
Disease Progression
Female
Follow-Up Studies
Gene Expression
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Homozygote
Humans
Hypoxia / complications
Hypoxia / genetics*
Hypoxia / physiopathology
Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
Male
Middle Aged
Models, Genetic
Polymorphism, Single Nucleotide*
Pulmonary Disease, Chronic Obstructive / complications
Pulmonary Disease, Chronic Obstructive / genetics*
Pulmonary Disease, Chronic Obstructive / physiopathology
Respiratory Function Tests
Risk Factors
Smoking / physiopathology
Spain
Vascular Endothelial Growth Factor A / genetics*
Vascular Endothelial Growth Factor Receptor-2 / genetics*

Substances

HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
VEGFA protein, human
Vascular Endothelial Growth Factor A
KDR protein, human
Vascular Endothelial Growth Factor Receptor-2

Grants and funding

This work was supported by Fondo de Investigación en Salud-Instituto Carlos III 09/00977, http://www.isciii.es/ISCIII/es/contenidos/fd-el-instituto/quienes-somos.shtml, author who received the funding: CC. Project was co-financed by the European Regional Development Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.