title: Shared genetic variants between serum levels of high-density lipoprotein cholesterol and wheezing in a cohort of children from Cyprus.
abstract: BACKGROUND
  In a cohort of children in Cyprus, we recently reported low levels of high density lipoprotein cholesterol (HDL-C) to be associated with asthma. We examined whether genetic polymorphisms that were previously linked individually to asthma, obesity, or HDL-C are associated with both asthma and HDL-C levels in the Cyprus cohort.
  
  
  METHODS
  We assessed genotypes frequencies in current-wheezers (n = 190) and non-asthmatic controls (n = 671) and HDL-C levels across several genotypes. Binary logistic regression models were used to assess the effect of genotypes on wheezing risk and examined whether this effect is carried out through changes of HDL-C.
  
  
  RESULTS
  Of the 16 polymorphisms tested, two polymorphisms TNFa rs3093664 and PRKCA rs9892651 presented significant differences in genotype distribution among current-wheezers and controls. Higher HDL-C levels were noted in carriers of genotype GG of polymorphism TNFa rs3093664 that was protective for wheezing Vs AG and AA genotypes (65.3 Vs 51.8 and 53.3 mg/dl, p-value < 0.001 and p-value for trend = 0.028). In polymorphism PRKCA rs9892651, HDL-C levels were lower in carriers of CC and TC genotypes that were more frequent in current-wheezers Vs TT genotype (52.2 and 52.7 Vs 55.2 mg/dl, p-value = 0.042 and p-value for trend = 0.02). The association of TNFa rs3093664 with wheezing is partly mediated by its effect on HDL-C whereas association of PRKCA rs9892651 with wheezing appeared to be independent of HDL-C.
  
  
  CONCLUSIONS
  We found evidence that two SNPs located in different genetic loci, are associated with both wheezing and HDL-C levels, although more studies in other populations are needed to confirm our results.
authors.affiliation: Medical School, University of Cyprus, Nicosia, Cyprus.|Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.
authors.forename: Panayiotis K
authors.initials: PK
authors.lastname: Yiallouros
authors.affiliation: Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus. panagiotis.kouis@cut.ac.cy.
authors.forename: Panayiotis
authors.identifier: http://orcid.org/0000-0003-0511-5352
authors.initials: P
authors.lastname: Kouis
authors.affiliation: Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.|Department of Nursing, School of Health Sciences, Cyprus University of Technology, Limassol, Cyprus.|St George University of London Medical School at the University of Nicosia, Nicosia, Cyprus.
authors.forename: Ourania
authors.initials: O
authors.lastname: Kolokotroni
authors.affiliation: Lebanese American University, School of Medicine, Beirut, Lebanon.
authors.forename: Sonia
authors.initials: S
authors.lastname: Youhanna
authors.affiliation: Research and Education Institute of Child Health, Nicosia, Cyprus.
authors.forename: Savvas C
authors.initials: SC
authors.lastname: Savva
authors.affiliation: Department of Biochemistry, Attikon University Hospital, Athens, Greece.
authors.forename: Kleanthi
authors.initials: K
authors.lastname: Dima
authors.affiliation: Department of Biochemistry, Attikon University Hospital, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Zerva
authors.affiliation: Lebanese American University, School of Medicine, Beirut, Lebanon.
authors.forename: Danielle
authors.initials: D
authors.lastname: Platt
authors.affiliation: Department of Nursing, School of Health Sciences, Cyprus University of Technology, Limassol, Cyprus.
authors.forename: Nicos
authors.initials: N
authors.lastname: Middleton
authors.affiliation: Lebanese American University, School of Medicine, Beirut, Lebanon.
authors.forename: Pierre
authors.initials: P
authors.lastname: Zalloua
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003535:Cyprus; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051571:Protein Kinase C-alpha / Q000235:genetics*; D012135:Respiratory Sounds; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D014409:Tumor Necrosis Factor-alpha; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha
keywords: Asthma; Children; Genotypes; High density lipoprotein cholesterol; Polymorphisms