Zalewski G, Ciccarone E, Di Castelnuovo A, Zito F, Capani F, de Gaetano G, Donati M B, Iacoviello L
Laboratory of Genetic and Environmental Epidemiology, Center for High Technology Research and Education in Biomedical Sciences, Catholic University, 86100 Campobasso, Italy.
Nutr Metab Cardiovasc Dis. 2006 Sep;16(6):418-25. doi: 10.1016/j.numecd.2005.07.002. Epub 2005 Dec 1.
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.
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).
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.
在包括糖尿病和缺血性心脏病在内的多种病症中，均发现参与白细胞与内皮细胞短暂黏附的选择素家族成员sP-选择素水平升高。已确定编码P-选择素的基因存在多种多态性。本研究的目的是探讨三种非同义P-选择素基因多态性，即Tyr715Pro、Asn562Asp和Ser290Asn，在2型糖尿病患者大血管并发症风险决定中的作用。
采用横断面病例对照设计，对837例意大利2型糖尿病患者进行研究，将301例至少有一次心绞痛（AP）、急性心肌梗死（AMI）、中风、短暂性脑缺血发作（TIA）或外周动脉疾病（PAD）发作的病例与536例在检查前无缺血性血管并发症的对照进行比较。病例组在检查时糖尿病病程更长，且比对照组年龄更大。病例组中高血压和男性比例过高。三种多态性变体的等位基因频率和基因型分布在病例组或对照组中均未显示出任何显著的优先关联。比值比也表明，即使在对潜在混杂变量进行调整后，对心血管疾病风险也没有影响。Tyr715Pro和Asn562Asp之间存在强烈的等位基因关联（D' = -0.99，P < 0.0001）。Ser290Asn与Tyr715Pro处于连锁不平衡状态（D' = 0.43，P = 0.15），与Asn562Asp几乎完全处于平衡状态（D' = 0.05，P = 0.5）。从基因型数据推断的单倍型相位显示存在6种单倍型。全局显著性检验表明病例组和对照组之间三种标记单倍型分布无差异（P = 0.88，自由度 = 5）。
本研究排除了Tyr715Pro、Asn562Asp和Ser290Asn P-选择素多态性对2型糖尿病缺血性血管并发症易感性的主要影响。
