title: Sex hormone alterations and systemic inflammation in a group of male COPD smokers and their correlation with the +138 insA/delA endothelin-1 gene polymorphism. A case-control study.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is characterized by the presence of a low-grade systemic inflammation that is implicated in the pathogenesis of numerous extrapulmonary manifestations, such as hypogonadism. Endothelin-1 (ET-1) is a molecule that demonstrates pro-inflammatory properties and can augment the airway and systemic inflammation. Single nucleotide polymorphisms (SNPs) of the ET-1 gene that increase ET-1 serum levels are an important area of investigation. We examined the alterations in inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and in the levels of testosterone, free testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a group of male COPD smokers when compared to their age-matched controls and how these alterations relate to the presence of a functional ET-1 SNP, the adenine insertion SNP +138 insA/delA.
  
  
  METHODS
  In this case control study, 80 male control smokers and 82 male COPD smokers were recruited for comparison. Among the male COPD smokers, 37 were carriers of the +138 insA/delA SNP. Two COPD subgroups according to genotype were formed: (1) A group of 45 males homozygous for the wild type allele (3A/3A) and (2) a group of 37 males heterozygous for the mutant allele (3A/4A).
  
  
  RESULTS
  Levels of testosterone and free testosterone were lower in the COPD group and even lower in the 3A/4A COPD group. CRP and ESR levels were higher in both COPD groups, but their elevation was statistically significant only for the 3A/4A COPD group. Testosterone and free testosterone levels correlated positively with PaO2 for both COPD groups. An inverse correlation between testosterone and CRP was demonstrated for the 3A/4A COPD subgroup.
  
  
  CONCLUSIONS
  Levels of testosterone correlated to FEV1, hypoxemia and weakly to CRP. The synchronous presence of the +138 insA/delA SNP resulted in even greater sex hormone level decline probably due to the presence of a more intense systemic inflammation.
authors.affiliation: Division of Pneumology, Department of Internal Medicine, University Hospital of Rio Patras, Greece. pneumonas@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Kaparianos
authors.forename: E
authors.initials: E
authors.lastname: Argyropoulou
authors.forename: G
authors.initials: G
authors.lastname: Efremidis
authors.forename: K
authors.initials: K
authors.lastname: Spiropoulos
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005541:Forced Expiratory Volume; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics*; D012907:Smoking / Q000097:blood*
chemical_list: D019332:Endothelin-1; D012739:Gonadal Steroid Hormones; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002097:C-Reactive Protein