Tabara Y, Kohara K, Nakura J, Miki T
Department of Geriatric Medicine, Ehime University School of Medicine, Japan.
J Hum Genet. 2001;46(5):278-84. doi: 10.1007/s100380170079.
The risk factor-gene interaction in carotid atherosclerosis was investigated in 205 community-dwelling healthy subjects aged 50 years or more in Japan. The intima-media thickness (IMT) of the common carotid artery was evaluated by ultrasonography with a 7.5-MHz probe. Gene polymorphisms were determined for each subject with angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C, and apolipoprotein E (apoE) genotypes. There was no genotype-specific difference in carotid IMT among any genes examined. Combinations of genotypes did not increase carotid IMT compared with subjects without these genotypes. In the total population, multiple regression analysis showed that age, systolic blood pressure (SBP), sex, and body mass index (BMI) were significantly associated with carotid IMT. However, the association between risk factors and IMT was genotype-specific. Age was significantly associated with IMT in ACE D carriers, but not in subjects with the ACE II genotype. Analysis of covariance adjusted with other risk factors showed that the age-dependent change in IMT was significantly different between subjects with the ACE II genotype and the ACE D carriers (F[1.196] = 4.97; P = 0.027). Similarly, the regression of IMT on SBP was significantly different between AGT TT and AGT MT + MM (F[1.196] = 7.20; P = 0.0079). The regression of IMT on BMI was also significantly different between apo E4 carriers and noncarriers (F[1.196] = 6.78; P = 0.0099). Furthermore, general linear model analysis with risk factors, genotype, and risk factor-genotype interactions revealed that the ageACE genotype interaction, the SBPAGT genotype interaction, and the BMI*apoE genotype interaction were significantly associated with IMT. These findings further support the role of risk factor-gene interaction in carotid atherosclerosis.
在日本205名年龄在50岁及以上的社区健康居民中，研究了颈动脉粥样硬化中的危险因素与基因的相互作用。使用7.5兆赫探头的超声检查评估颈总动脉的内膜中层厚度（IMT）。确定了每位受试者的血管紧张素转换酶（ACE）插入/缺失（I/D）、血管紧张素原（AGT）M235T、血管紧张素II 1型受体（AT1R）A1166C和载脂蛋白E（apoE）基因型。在所检测的任何基因中，颈动脉IMT均无基因型特异性差异。与没有这些基因型的受试者相比，基因型组合并未增加颈动脉IMT。在总人群中，多元回归分析表明，年龄、收缩压（SBP）、性别和体重指数（BMI）与颈动脉IMT显著相关。然而，危险因素与IMT之间的关联具有基因型特异性。年龄与ACE D携带者的IMT显著相关，但与ACE II基因型的受试者无关。经其他危险因素校正的协方差分析表明，ACE II基因型受试者和ACE D携带者之间IMT的年龄依赖性变化显著不同（F[1.196]=4.97；P=0.027）。同样，AGT TT与AGT MT+MM之间IMT对SBP的回归也显著不同（F[1.196]=7.20；P=0.0079）。apo E4携带者与非携带者之间IMT对BMI的回归也显著不同（F[1.196]=6.78；P=0.0099）。此外，对危险因素、基因型和危险因素-基因型相互作用进行的一般线性模型分析表明，年龄ACE基因型相互作用、SBPAGT基因型相互作用和BMI*apoE基因型相互作用与IMT显著相关。这些发现进一步支持了危险因素-基因相互作用在颈动脉粥样硬化中的作用。
