title: TNFRSF11B gene polymorphisms increased risk of peripheral arterial occlusive disease and critical limb ischemia in patients with type 2 diabetes.
abstract: OBJECTIVE
  Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. OPG has been hypothesized to modulate vascular functions; however, its role in mediating atherosclerosis is controversial. Epidemiological data in patients with cardiovascular disease (CVD) indicate that OPG serum levels are associated with several inflammatory markers, myocardial infarction events, and calcium scores, suggesting that OPG may be causative for CVD.
  
  
  METHODS
  The present study aimed to evaluate whether the OPG gene (TNFRSF11B) polymorphisms are involved in the development of peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI) in patients with type 2 diabetes. This genetic association study included 402 diabetic patients (139 males and 263 females) with peripheral arterial occlusive disease and 567 diabetic subjects without peripheral arterial occlusive disease (208 males and 359 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism.
  
  
  RESULTS
  We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (27.9 vs. 12.2 %, P < 0.01; 33.6 vs. 10.4 %, P < 0.01 and 24.4 vs. 12.7 %, P < 0.01, respectively) and independently (adjusted OR 4.97 (3.12-6.91), OR 7.02 (4.96-11.67), and OR 2.85 (1.95-4.02), respectively) associated with PAOD. We also found that these three polymorphisms act synergistically in patients with PAOD and are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes carried concomitantly by a given individual.
  
  
  CONCLUSIONS
  The TNFRSF11B gene polymorphisms under study are associated with PAOD, and synergistic effects between these genotypes might be potential markers for the presence and severity of atherosclerotic disorders.
authors.affiliation: Institute of Rheumatology and Affine Sciences, Catholic University School of Medicine, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Biscetti
authors.forename: Carlo Filippo
authors.initials: CF
authors.lastname: Porreca
authors.forename: Flavio
authors.initials: F
authors.lastname: Bertucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Straface
authors.forename: Angelo
authors.initials: A
authors.lastname: Santoliquido
authors.forename: Paolo
authors.initials: P
authors.lastname: Tondi
authors.forename: Flavia
authors.initials: F
authors.lastname: Angelini
authors.forename: Dario
authors.initials: D
authors.lastname: Pitocco
authors.forename: Luca
authors.initials: L
authors.lastname: Santoro
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Landolfi
authors.forename: Andrea
authors.initials: A
authors.lastname: Flex
mesh_terms: D000368:Aged; D001157:Arterial Occlusive Diseases / Q000453:epidemiology / Q000235:genetics*; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics; D005121:Extremities / Q000098:blood supply*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007511:Ischemia / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human