Association of the Lewis genotype with cardiovascular risk factors and subclinical carotid atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study
Association of the Lewis genotype with cardiovascular risk factors and subclinical carotid atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study
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DOI：
10.1046/j.1365-2796.2003.01263.x
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发表时间：
2004-01-01
影响因子：
11.1
通讯作者：
Weston, BW
中科院分区：
文献类型：
--
作者：
Cakir, B;Heiss, G;Weston, BW
目标.探讨刘易斯基因型与心血管病主要危险因素及颈动脉内膜中层厚度（IMT）的关系。刘易斯基因分型包括刘易斯（FUT 3）基因在核苷酸位置59、1067、202和314处的四个主要突变。两项互补的基于人群的横断面研究。社区动脉粥样硬化风险（ARIC）研究。在761名年龄在45-64岁的男性和女性中研究了刘易斯基因型与主要心血管危险因素之间的关系，这些男性和女性没有已知的临床动脉粥样硬化疾病; 577名是白人，184名是非洲裔美国人。在419名颈动脉IMT>1.0 mm的个体和819名对照者中研究了刘易斯基因型与亚临床颈动脉粥样硬化的关系。按刘易斯基因型列出的心血管危险因素的平均值。亚临床颈动脉粥样硬化病例和对照者的刘易斯基因型频率。与具有Lewis阳性基因型的对应者相比，具有与缺乏α（1，3/1，4）-岩藻糖基转移酶活性一致的刘易斯基因型的个体（即Lewis阴性基因型）具有统计学显著性较低的空腹血糖、因子VIII c、血管性血友病因子和舒张压。刘易斯基因型和单倍型在颈动脉IMT>1.0 mm的个体（例）和对照组之间的分布无显著差异。在控制年龄、性别和种族/ARIC中心的情况下，与Lewis阳性基因型个体相比，Lewis阴性基因型携带者颈动脉粥样硬化的几率为1.23（95%可信区间0.70-2.16）。在我们的数据中，刘易斯“基因型”和亚临床动脉粥样硬化之间缺乏统计学显著相关性，这表明早期研究报告的“表型”水平的相关性可能反映了刘易斯系统生物学的各个方面，而不是固有的遗传特性。
Objectives. To evaluate the relationship of Lewis genotypes with major cardiovascular risk factors and the intima-media thickness (IMT) of carotid arteries. Lewis genotyping included four major mutations of the Lewis (FUT3) gene at nucleotide positions 59, 1067, 202 and 314.Design. Two complementary population-based cross-sectional studies.Setting. The Atherosclerosis Risk in Communities (ARIC) Study.Subjects. The relationship between Lewis genotype and major cardiovascular risk factors was studied in 761 men and women aged 45-64 years without known clinical atherosclerotic disease; 577 were Caucasians and 184 were African-Americans. The association of Lewis genotype and subclinical carotid atherosclerosis was studied in 419 individuals with, and 819 controls without carotid IMT of >1.0 mm, measured by B-mode ultrasound.Main outcome measures. Mean values of cardiovascular risk factors by Lewis genotype. Lewis genotype frequencies in subclinical carotid atherosclerosis cases and controls.Results. Individuals with Lewis genotypes consistent with lack of alpha(1,3/1,4)-fucosyltransferase activity (i.e. Lewis-negative genotype) had statistically significantly lower fasting glucose, factor VIIIc, von Willebrand factor and diastolic blood pressure compared with their counterparts with Lewis-positive genotypes. The distribution of Lewis genotypes and haplotypes was not significantly different between individuals with carotid IMT of >1.0 mm (cases) and their controls. The odds of carotid atherosclerosis in carriers of the Lewis-negative genotype was 1.23 (95% confidence interval 0.70-2.16) compared to individuals with Lewis-positive genotype, controlling for age, gender and race/ARIC field centre.Conclusion. The lack of a statistically significant association between Lewis 'genotype' and subclinical atherosclerosis in our data suggests that earlier studies reporting associations at the 'phenotypic' level may reflect aspects of the biology of the Lewis system other than an inherent genetic property.