title: +9/+9 Homozygosity of the bradykinin receptor gene polymorphism is associated with reduced fat-free mass in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  The etiology of muscle wasting in chronic obstructive pulmonary disease (COPD) is incompletely understood. We previously showed that the D rather than the I polymorphic variant of the angiotensin-converting enzyme (ACE) gene is associated with preserved quadriceps strength in COPD. If the ACE D allele influences skeletal muscle through increased ACE-related kinin degradation [and reduced activity at the bradykinin type 2 receptor (BK(2)R)], we might expect a similar association with the +9 BK(2)R genotype in this population as well.
  
  
  OBJECTIVE
  The objective was to test the hypothesis that the BK(2)R gene polymorphism is a determinant of fat-free mass and quadriceps strength in patients with COPD.
  
  
  METHODS
  In a cross-sectional design we determined BK(2)R genotype, fat-free mass, and quadriceps strength in 110 COPD patients with a mean (+/-SD) predicted forced expiratory volume in 1 s of 34.3 +/- 16.4% and in 104 healthy age-matched control subjects.
  
  
  RESULTS
  The mean (+/-SD) fat-free mass index (in kg/m(2)) was significantly lower in 37 patients homozygous for the +9 allele than in carriers of the -9 allele (15.7 +/- 1.8 compared with 16.7 +/- 2.3; P = 0.038); the same pattern was true for quadriceps maximal voluntary force (30.8 +/- 10.4 and 36.4 +/- 12.8 kg; P = 0.02), respectively. No significant effect of BK(2)R genotype on inspiratory muscle strength or on any variable in control subjects was observed. There was no interaction between the effect of the BK(2)R and ACE genotypes on quadriceps strength.
  
  
  CONCLUSIONS
  The genotype associated with reduced BK(2)R expression is associated with reduced fat-free mass and quadriceps strength in COPD. However, alterations in the activity at the BK(2)R do not seem to account for the previously identified association of quadriceps strength with ACE genotype.
authors.affiliation: Respiratory Muscle Laboratory, Royal Brompton Hospital, Fulham Road, London SW3 6NP, United Kingdom. n.hopkinson@ic.ac.uk
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.forename: Kyriacos I
authors.initials: KI
authors.lastname: Eleftheriou
authors.forename: John
authors.initials: J
authors.lastname: Payne
authors.forename: Annabel H
authors.initials: AH
authors.lastname: Nickol
authors.forename: Emma
authors.initials: E
authors.lastname: Hawe
authors.forename: John
authors.initials: J
authors.lastname: Moxham
authors.forename: Hugh
authors.initials: H
authors.lastname: Montgomery
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology*; D018002:Receptors, Bradykinin / Q000235:genetics* / Q000378:metabolism*; D012129:Respiratory Function Tests; D012132:Respiratory Muscles / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018002:Receptors, Bradykinin; D007703:Peptidyl-Dipeptidase A