Yamada Yoshiji, Kato Kimihiko, Oguri Mitsutoshi, Yoshida Tetsuro, Yokoi Kiyoshi, Watanabe Sachiro, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Ichihara Sahoko, Aoyagi Yukitoshi, Yasunaga Akitomo, Park Hyuntae, Tanaka Masashi, Nozawa Yoshinori
FAHA, Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Mie 514-8507, Japan.
Int J Mol Med. 2008 Jun;21(6):801-8.
Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. Among these polymorphisms, the 2445G-->A (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.
代谢综合征是心血管疾病的一个危险因素。本研究的目的是在代谢综合征患者中鉴定出易患动脉粥样硬化性脑梗死的基因变异，以便预测这种疾病的遗传风险。研究人群包括1284名无亲缘关系的日本代谢综合征患者，其中313例为动脉粥样硬化性脑梗死患者，971例为对照。采用聚合酶链反应和序列特异性寡核苷酸探针结合悬浮芯片技术的方法，对202个候选基因的296个多态性位点进行基因分型。卡方检验、对年龄、性别、体重指数以及高血压、高胆固醇血症和糖尿病患病率进行校正的多变量逻辑回归分析，以及逐步向前选择程序显示，FABP2的2445G→A（Ala54Thr）多态性（rs1799883）、IPF1的-108/3G→4G多态性（S82168）、FABP1的A→G（Thr94Ala）多态性（rs2241883）、ROS1的G→A（Asp2213Asn）多态性（rs529038）、ADIPOQ的-11377C→G多态性（rs266729）、ALOX5AP的162A→C多态性（rs4769055）、NOS3的-786T→C多态性（rs2070744）以及LGALS2的3279C→T多态性（rs7291467）与动脉粥样硬化性脑梗死的患病率相关（P<0.05）。在这些多态性中，FABP2的2445G→A（Ala54Thr）多态性与这种疾病的相关性最为显著。我们的结果表明，FABP2、IPF1、FABP1、ROS1、ADIPOQ、ALOX5AP、NOS3和LGALS2是日本代谢综合征患者动脉粥样硬化性脑梗死的易感基因座。这些多态性的基因型，尤其是FABP2的2445G→A（Ala54Thr）多态性，可能对预测这类个体动脉粥样硬化性脑梗死的遗传风险具有指导意义。
