Zee R Y, Lou Y K, Morris B J
Department of Physiology, University of Sydney, New South Wales, Australia.
J Hypertens Suppl. 1994;12(7):S13-22.
To determine whether a microsatellite polymorphism of the insulin receptor gene (INSR) is associated with essential hypertension, as has been demonstrated previously for an RsaI restriction fragment length polymorphism (RFLP), and to examine blood pressure and plasma lipid profiles in relation to genotype.
The study involved 75 Caucasian, non-diabetic hypertensive patients whose parents were both hypertensive, and 75 age-matched normotensive subjects whose parents were each normotensive after the age of 50 years. Genotypes for the microsatellite polymorphism were determined for each subject using leucocyte DNA and a polymerase chain reaction method. Other parameters, including pretreatment blood pressure, body mass index and plasma lipids, were also determined.
Comparison of microsatellite data for the eight genotypes and four alleles that were detected showed no significant difference by chi 2 analysis, either between the hypertensive and normotensive groups, or between obese and non-obese subgroups of hypertensives. This is in contrast to the significantly higher frequency seen for the R1- allele of an RsaI RFLP of INSR: 0.71 in the hypertensive group compared with 0.56 in the normotensive group. R1- allele frequency was elevated in all age groups of hypertensives and did not differ between obese and non-obese subgroups. The non-obese hypertensives also had different plasma lipid profiles according to genotypes of the RFLP, with higher total and low-density lipoprotein-cholesterol in patients having the hypertension-associated R1- allele of the intron 9 polymorphism. Moreover, systolic blood pressure was significantly greater in patients carrying the R1- allele and aged > or = 60 years.
The present study allows definition of the hypertension-associated variants of INSR as those which are in linkage disequilibrium with a (CA)-repeat insertion polymorphism in intron 9 of the large, 22 exon, > 120-kb gene, but not those associated with a polymorphism in the second intron.
如先前已证实在胰岛素受体基因（INSR）的RsaI限制性片段长度多态性（RFLP）中那样，确定INSR的微卫星多态性是否与原发性高血压相关，并研究血压和血脂谱与基因型的关系。
该研究纳入了75名白种人非糖尿病高血压患者，其父母均为高血压患者，以及75名年龄匹配的血压正常受试者，其父母在50岁后血压均正常。使用白细胞DNA和聚合酶链反应方法为每个受试者确定微卫星多态性的基因型。还测定了其他参数，包括治疗前血压、体重指数和血脂。
对检测到的8种基因型和4个等位基因的微卫星数据进行比较，通过卡方分析显示，高血压组与血压正常组之间，或高血压患者的肥胖与非肥胖亚组之间均无显著差异。这与INSR的RsaI RFLP的R1 - 等位基因频率显著更高形成对比：高血压组为0.71，血压正常组为0.56。高血压患者的所有年龄组中R1 - 等位基因频率均升高，且肥胖与非肥胖亚组之间无差异。非肥胖高血压患者根据RFLP的基因型也有不同的血脂谱，内含子9多态性中与高血压相关的R1 - 等位基因的患者总胆固醇和低密度脂蛋白胆固醇更高。此外，携带R1 - 等位基因且年龄≥60岁的患者收缩压显著更高。
本研究能够将INSR与高血压相关的变异定义为与大型22外显子、>120 kb基因的内含子9中的（CA）重复插入多态性处于连锁不平衡的变异，而非与第二个内含子中的多态性相关的变异。
