Vitamin D receptor genotypes influence quadriceps strength in chronic obstructive pulmonary disease

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. Design: Vitamin D receptor Fokl 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) over bar +/- SD forced expiratory volume in 1 s (FEV1): 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 Fokl polymorphism had less quadriceps strength than did those with :I 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 Bsml on quadriceps strength was least apparent in patients with the ACE H 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 Bsml polymorphism is associated with strength only in patients.