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American Journal of Clinical Nutrition, Vol. 87, No. 2, 385-390, February 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Vitamin D receptor genotypes influence quadriceps strength in chronic obstructive pulmonary disease1,2,3

Nicholas S Hopkinson, Ka Wah Li, Anthony Kehoe, Steve E Humphries, Michael Roughton, John Moxham, Hugh Montgomery and Michael I Polkey

1 From the Respiratory Muscle Laboratory, Royal Brompton Hospital, London, United Kingdom (NSH and MIP); the Centre for Cardiovascular Genetics, Royal Free and UCL Medical School, Rayne Institute, London, United Kingdom (KWL and SEH); the UCL Institute for Human Health and Performance, London, United Kingdom (AK and HM); the National Heart and Lung Institute, Imperial College, London, United Kingdom (NSH, MR, and MIP); and the Department of Respiratory Medicine, King's College Hospital, London, United Kingdom (JM)

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 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 (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 FokI polymorphism had less quadriceps strength than did those with ≥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.

Key Words: Muscle • quadriceps • angiotensin-converting enzyme • bradykinin






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