TY - JOUR
T1 - P-selectin gene genotypes or haplotypes and cardiovascular complications in type 2 diabetes mellitus
AU - Zalewski, G.
AU - Ciccarone, E.
AU - Di Castelnuovo, A.
AU - Zito, F.
AU - Capani, F.
AU - de Gaetano, G.
AU - Donati, M. B.
AU - Iacoviello, L.
AU - on behalf of the GENDIABE investigators, behalf of the GENDIABE investigators
PY - 2006/9
Y1 - 2006/9
N2 - Background and aim: Increased levels of sP-selectin, a member of the selectin family involved in the transient attachment of leukocytes to endothelial cells, are found in a number of conditions including diabetes and ischemic heart disease. A number of polymorphisms in the gene encoding P-selectin have been identified. The purpose of the present study was to explore the role of three non-synonymous P-selectin gene polymorphisms, Tyr715Pro, Asn562Asp and Ser290Asn, in determining the risk of macrovascular complications in type 2 diabetic patients. Methods and results: Following a cross-sectional case-control design from 837 Italian type 2 diabetics, 301 cases with at least one episode of angina pectoris (AP), acute myocardial infarction (AMI), stroke, transient ischemic attacks (TIA) or peripheral arterial disease (PAD) were compared with 536 controls free of ischemic vascular complications in the period preceding the examination. Case subjects had longer duration of diabetes at the time of examination and were older as compared with controls. Hypertension and male sex were over-represented among cases. Allele frequency and genotype distribution of the three polymorphic variants did not show any significant preferential association in groups of cases or controls. Odds ratios also indicated no effect on risk of cardiovascular disease even after adjustment for potentially confounding variables. There was a strong allelic association between Tyr715Pro and Asn562Asp (D′ = -0.99, P <0.0001). Ser290Asn was in linkage disequilibrium with Tyr715Pro (D′ = 0.43, P = 0.15) and in almost complete equilibrium with Asn562Asp (D′ = 0.05, P = 0.5). Haplotype phase inferred from genotypic data revealed the presence of 6 haplotypes. Global test of significance showed no difference in three marker haplotype distribution between cases and controls (P = 0.88, df = 5). Conclusions: The present study excludes a major contribution of Tyr715Pro, Asn562Asp and Ser290Asn P-selectin polymorphisms to a susceptibility to ischemic vascular complications in type 2 diabetes.
AB - Background and aim: Increased levels of sP-selectin, a member of the selectin family involved in the transient attachment of leukocytes to endothelial cells, are found in a number of conditions including diabetes and ischemic heart disease. A number of polymorphisms in the gene encoding P-selectin have been identified. The purpose of the present study was to explore the role of three non-synonymous P-selectin gene polymorphisms, Tyr715Pro, Asn562Asp and Ser290Asn, in determining the risk of macrovascular complications in type 2 diabetic patients. Methods and results: Following a cross-sectional case-control design from 837 Italian type 2 diabetics, 301 cases with at least one episode of angina pectoris (AP), acute myocardial infarction (AMI), stroke, transient ischemic attacks (TIA) or peripheral arterial disease (PAD) were compared with 536 controls free of ischemic vascular complications in the period preceding the examination. Case subjects had longer duration of diabetes at the time of examination and were older as compared with controls. Hypertension and male sex were over-represented among cases. Allele frequency and genotype distribution of the three polymorphic variants did not show any significant preferential association in groups of cases or controls. Odds ratios also indicated no effect on risk of cardiovascular disease even after adjustment for potentially confounding variables. There was a strong allelic association between Tyr715Pro and Asn562Asp (D′ = -0.99, P <0.0001). Ser290Asn was in linkage disequilibrium with Tyr715Pro (D′ = 0.43, P = 0.15) and in almost complete equilibrium with Asn562Asp (D′ = 0.05, P = 0.5). Haplotype phase inferred from genotypic data revealed the presence of 6 haplotypes. Global test of significance showed no difference in three marker haplotype distribution between cases and controls (P = 0.88, df = 5). Conclusions: The present study excludes a major contribution of Tyr715Pro, Asn562Asp and Ser290Asn P-selectin polymorphisms to a susceptibility to ischemic vascular complications in type 2 diabetes.
KW - Cardiovascular disease
KW - Diabetes
KW - Haplotypes
KW - P-selectin
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U2 - 10.1016/j.numecd.2005.07.002
DO - 10.1016/j.numecd.2005.07.002
M3 - Article
C2 - 16935700
AN - SCOPUS:33747803921
VL - 16
SP - 418
EP - 425
JO - Nutrition, Metabolism and Cardiovascular Diseases
JF - Nutrition, Metabolism and Cardiovascular Diseases
SN - 0939-4753
IS - 6
ER -