Atorvastatin and BMD in Coronary Syndrome. Role of Lys656Asn Polymorphism of Leptin Receptor Gene

Abstract

Abstract. Objectives. To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome according to the Lys656Asn leptin receptor gene polymorphism. Methods. Sixty-two patients with acute coronary syndrome were included. Patients were allocated to low and high doses of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk and were studied at hospital admission and at 12 months. 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 and hip. Patients with a T-score<-2.5 were considered osteoporotic. The Lys656Asn leptin receptor gene polymorphism was determined by PCR. Results. Forty-two patients were Lys/Lys homozygotic and 20 Lys/Asn heterozygotic. The prevalence of osteoporosis was 31% for the Lys/Lys genotype and 27% for the Lys/Asn genotype with no significant differences between groups. There was a significant increase in bone mineral density in the lumbar spine (1.117 ± 0.24 versus 1.135 ± 0.24, P = 0.008) in patients with the Lys/Lys genotype. Conclusion. Atorvastatin increases lumbar spine bone mineral density only in patients with the Lys/Lys genotype of the Lys656Asn polymorphism. . Inflammatory cytokines play an important role in the imbalance between bone formation and resorption that leads to the reduced bone mass seen in osteoporosis [3]. In addition, drugs such as statins are effective in both diseases, diminishing vascular events in patients with atherosclerosis and increasing bone mass in those with high levels of cholesterol [4]. Human leptin is a protein of 167 amino acids manufactured in fat cells which is involved in regulating the ingestion and consumption of energy. It intervenes in the regulation of bone mass by means of a central hypothalamic mechanism, exerting a double antagonistic effect on bone formation and resorption through activation of the sympathetic nervous system and the Cocaine Amphetamine Regulated Transcript (CART) [5]. In addition, studies have shown that hyperleptinemia can exert atherogenic effects [6]. In North American patients, elevated leptin levels have been associated with an increased risk of myocardial infarction in both males (3.16, 95% CI 1.40-7.37) and females (3.95, 95% CI 1.29-12.72) [7].Leptin exerts its biological effect by bonding with a receptor from the cytokine-receptor family. The leptin

Pharmacogenomics-based systematic review of coronary artery disease based on personalized medicine procedure

“…Compared to these genes, 11 genes have unknown clinical trials including ABCG8, AGT, APOB, CYP2B6, CYP2C9, FABP1, KDR, NPPA, NR3C2, NT5C2 , and PTGS1 which are highly suggested for future clinical trials of investigating the related drugs with CAD. Some of these genes had limited studies with pharmacology of CAD including ALDH2 [ 67 ], APOC1 ([ 68 ]), FMO3 [ 69 ], LEPR [ 70 ], P2RY12 [ 71 ], SCARB1 [ 72 ], SH2B3 [ 73 ], SLCO1B1 [ 74 ], TLR4 [ 75 ], EDN1 [ 76 ], NOS3 [ 77 ], ABCG8 [ 78 ], AGT [ 79 ], FABP1 [ 80 ], KDR [ 81 ], NPPA [ 82 ], NR3C2 [ 83 ], NT5C2 [ 84 ], and PTGS1 [ 85 ].…”

The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in rheumatologic disorders: a comprehensive review

“…Recently, researchers have identiWed speciWc polymorphisms in the tumor necrosis factor-alpha and leptin receptor genes, respectively, that have been linked to increased lumbar spine bone mineral density with statin use [41,42]. Additionally, studies have shown that in women treated with biphosphonates or hormone replacement therapy, concurrent statin use results in a greater increase in bone mineral density and reduction in skeletal fracture risk, suggesting a synergistic drug eVect [43][44][45].…”