title: Vitamin D receptor genotypes influence quadriceps strength in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Quadriceps weakness is an important complication of chronic obstructive pulmonary disease (COPD) and is associated with impaired exercise capacity and greater mortality. Its etiology is multifactorial, and evidence is growing that it is partly determined by genetic susceptibility.
  
  
  OBJECTIVE
  Using an established cohort, we tested whether quadriceps weakness in patients with COPD is influenced by common variations in the gene for the vitamin D receptor.
  
  
  METHODS
  Vitamin D receptor FokI and BsmI genotypes and the (I/D) angiotensin-converting enzyme (ACE) and bradykinin receptor (+9/-9) genotypes were identified in 107 patients with stable COPD [x +/- SD forced expiratory volume in 1 s (FEV(1)): 34.5 +/- 16.5] and 104 healthy, age-matched control subjects. Quadriceps maximum voluntary contraction force and fat-free mass assessed by bioelectrical impedance analysis were measured.
  
  
  RESULTS
  After adjustment for covariables, both patients and control subjects who were homozygous for the C allele of the FokI polymorphism had less quadriceps strength than did those with > or =1 T allele [41.0 +/- 11.8 compared with 46.0 +/- 13.2 kg (P = 0.01) and 32.5 +/- 11.2 compared with 36.2 +/- 13.1 kg (P = 0.005), respectively]. The b allele of the BsmI polymorphism was associated with greater quadriceps strength in patients-37.0 +/- 13.3, 33.8 +/- 11.6, and 33.8 +/- 11.6 kg for bb, bB, and BB, respectively (P = 0.0005)-but had no effect in healthy control subjects. The effect of BsmI on quadriceps strength was least apparent in patients with the ACE II genotype (P = 0.003).
  
  
  CONCLUSIONS
  The FokI common variants in the VDR gene are associated with skeletal muscle strength in both patients and control subjects, whereas the BsmI polymorphism is associated with strength only in patients.
authors.affiliation: Respiratory Muscle Laboratory, Royal Brompton Hospital, London, United Kingdom. n.hopkinson@ic.ac.uk
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.forename: Ka Wah
authors.initials: KW
authors.lastname: Li
authors.forename: Anthony
authors.initials: A
authors.lastname: Kehoe
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Michael
authors.initials: M
authors.lastname: Roughton
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: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D017097:Electric Impedance; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D053580:Muscle Strength; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000503:physiopathology*; D018002:Receptors, Bradykinin / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018002:Receptors, Bradykinin; D018167:Receptors, Calcitriol; C053864:endodeoxyribonuclease BsmI; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific; D007703:Peptidyl-Dipeptidase A