title: Smoking impairs and circulating stem cells favour the protective effect of the T allele of the connexin37 gene in ischemic heart disease--A multinational study.
abstract: BACKGROUND
  The connexin 37 (Cx37) gene is considered to be a candidate gene for ischemic heart disease (IHD). We analyzed the association between the C1019 > T (Pro319 > Ser) variant of the Cx37 gene and IHD in patients in the Czech Republic, Croatia, Hungary and Romania with regard to the presence/absence of selected cardiovascular risk factors (RF). In a complementary study, we analyzed the association between the Cx37 gene and circulating stem and endothelial progenitor cells in healthy women.
  
  
  METHODS
  The study population comprised 2396 patients (663 women) with IHD. The control population comprised 2476 subjects (1, 337 women). Additionally, in 662 healthy women, the association between the Cx37 gene and circulating stem and endothelial progenitor cells was analyzed.
  
  
  RESULTS
  The strongest protective effect of the Cx37 T allele was detected in non-smoking patients without diabetes mellitus and hypertension (OR 0.610, 95% CI 0.377-0.990); a similar effect was found in non-smoking men (OR 0.781, 95% CI 0.628-0.971); weaker effect was found in non-smoking women (OR 0.768, 95% CI 0.560-1.050). In non-smoking healthy women, stem cells were significantly higher in TT than in CT and CC carriers (p for trend 0.011). Additionally, non-smoking TT carriers had significantly higher number of stem cells than past and current smoking TT carriers (p for trend = 0.006); no such trend was found in CT and CC carriers.
  
  
  CONCLUSIONS
  The protective effect of the T allele of the Cx37 gene might be strongly modified by smoking; in women, this effect could be mediated through stem cells.
authors.affiliation: Center for Experimental Medicine, Laboratory for Atherosclerosis Research, Institute for Clinical & Experimental Medicine, Prague, Czech Republic. Electronic address: japi@medicon.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Pitha
authors.affiliation: Center for Experimental Medicine, Laboratory for Atherosclerosis Research, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Králová Lesná
authors.affiliation: Center for Experimental Medicine, Laboratory for Atherosclerosis Research, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.
authors.forename: Jaroslav A
authors.initials: JA
authors.lastname: Hubáček
authors.affiliation: Department of Clinical and Transplant Immunology, Institute of Clinical & Experimental Medicine, Prague, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Sekerková
authors.affiliation: Medicine Statistic Unit, Institute of Clinical & Experimental Medicine, Prague, Czech Republic.
authors.forename: Věra
authors.initials: V
authors.lastname: Lánská
authors.affiliation: Department of Preventive Cardiology, Institute of Clinical & Experimental Medicine, Prague, Czech Republic.
authors.forename: Věra
authors.initials: V
authors.lastname: Adámková
authors.affiliation: University of Medicine and Pharmacy "Carol Davila" Bucharest, Romania Emergency Clinical Hospital of Bucharest, Cardiology Dept., Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Dorobantu
authors.affiliation: Emergency Clinical Hospital of Bucharest, Cardiology Dept., Romania.
authors.forename: Rodica
authors.initials: R
authors.lastname: Nicolescu
authors.affiliation: Department of Cardiovascular Disease and Intensive Care, Osijek University Hospital, Osijek, Croatia.
authors.forename: Robert
authors.initials: R
authors.lastname: Steiner
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, University of Osijek, Osijek, Croatia.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Ivić
authors.affiliation: Regional Cooperation for Health, Science and Technology (RECOOP HST) Association, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Borbely
authors.affiliation: Regional Cooperation for Health, Science and Technology (RECOOP HST) Association, Debrecen, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Papp
authors.affiliation: Regional Cooperation for Health, Science and Technology (RECOOP HST) Association, Debrecen, Hungary; International Research and Innovation Management Program, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors.forename: Sandor G
authors.initials: SG
authors.lastname: Vari
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects*; D013234:Stem Cells / Q000166:cytology*; D000097006:Gap Junction alpha-4 Protein
chemical_list: D017630:Connexins; D004247:DNA; D000097006:Gap Junction alpha-4 Protein
keywords: Cardiovascular risk factors; Connexin37 gene; Endothelial progenitor cells; Ischemic heart disease; Sex; Stem cells