Effect of the TNFalpha-308 G/A polymorphism on the changes produced by atorvastatin in bone mineral density in patients with acute coronary syndrome

Ann Nutr Metab. 2008;53(2):117-21. doi: 10.1159/000170886. Epub 2008 Nov 10.

Abstract

Aims: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome depending on the tumor necrosis factor-alpha (TNFalpha)-308 G/A polymorphism.

Methods: Sixty-two patients with acute coronary syndrome (35 males and 27 females), average age 60 +/- 10 years, were included. Patients were given low (10-20 mg) and high doses (40-80 mg) atorvastatin according to their baseline levels of cholesterol and triglycerides and their index of vascular risk. Patients were studied during hospital admission (baseline) and at 12 months of follow-up. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow-up. Densitometric studies were conducted in the lumbar spine (L(2)-L(4)), femoral neck and trochanter using an X-ray densitometer. The TNFalpha-308 G/A polymorphism was determined by the polymerase chain reaction.

Results: Forty-five patients were homozygous for G/G (72.5%) and 17 were heterozygous for G/A (27.5%). The prevalence of osteoporosis (T score < or = 2.5 in the lumbar spine and/or hip) was 33% for the G/G genotype and 35% for the G/A genotype, with no statistically significant differences between groups. There was a statistically significant increase in bone mineral density (BMD) in the lumbar spine (1.107 +/- 0.32 vs. 1.129 +/- 0.23; p = 0.0001) in patients with the G/G genotype. No changes were observed in patients with the G/A genotype.

Conclusion: In patients with acute coronary syndrome, atorvastatin increases lumbar spine BMD solely in patients with the G/G genotype of the TNFalpha-308 G/A polymorphism.

MeSH terms

  • Absorptiometry, Photon / methods
  • Acute Coronary Syndrome / drug therapy
  • Amino Acids / urine
  • Anticholesteremic Agents / adverse effects*
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • Bone Density / drug effects*
  • Calcium / blood
  • Cholesterol / blood
  • Dose-Response Relationship, Drug
  • Female
  • Femur Neck / drug effects
  • Femur Neck / metabolism
  • Follow-Up Studies
  • Genotype
  • Heptanoic Acids / adverse effects*
  • Heptanoic Acids / therapeutic use
  • Humans
  • Magnesium / blood
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Osteoporosis / epidemiology*
  • Phosphorus / blood
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic*
  • Pyrroles / adverse effects*
  • Pyrroles / therapeutic use
  • Risk Factors
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Amino Acids
  • Anticholesteremic Agents
  • Heptanoic Acids
  • Pyrroles
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Osteocalcin
  • Phosphorus
  • deoxypyridinoline
  • Cholesterol
  • Atorvastatin
  • Magnesium
  • Calcium