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


CONCLUSIONS
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.
Pérez-Castrillón
José Luis
JL
Department of Internal Medicine, Rio Hortega University Hospital, Faculty of Medicine, Valladolid, Spain. castrv@terra.es
Vega
Gemma
G
Abad
Laura
L
Sanz-Cantalapiedra
Alberto
A
Gonzalez Sagredo
Manuel
M
de Luis
Daniel
D
Duenas-Laita
Antonio
A
D015502:Absorptiometry, Photon / Q000379:methods; D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000596:Amino Acids / Q000652:urine; D000924:Anticholesteremic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069059:Atorvastatin; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005272:Femur Neck / Q000187:drug effects / Q000378:metabolism; D005500:Follow-Up Studies; D005838:Genotype; D006538:Heptanoic Acids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000453:epidemiology*; D010758:Phosphorus / Q000097:blood; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000596:Amino Acids; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D010758:Phosphorus; C036020:deoxypyridinoline; D002784:Cholesterol; D000069059:Atorvastatin; D008274:Magnesium; D002118:Calcium