Benjafield A V, Jeyasingam C L, Nyholt D R, Griffiths L R, Morris B J
Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, University of Sydney, Sydney, New South Wales, Australia.
Hypertension. 1998 Dec;32(6):1094-7. doi: 10.1161/01.hyp.32.6.1094.
-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.
原发性高血压患者通过百日咳毒素敏感的G蛋白表现出增强的信号转导。G蛋白β3亚基基因（GNB3）第10外显子中C825T变体的T等位基因诱导形成一种活性增强的剪接变体（Gbeta3-s）。最近发现，在未经选择的德国患者中，GNB3的T等位基因与高血压有关（频率=0.31，而对照组为0.25）。为了在不同背景下证实并扩展这一发现，我们在澳大利亚白人高血压患者中进行了一项关联研究。这涉及一个经过广泛检查的队列，其中包括110名高血压患者（他们均为2名高血压父母的后代）和189名血压正常者（其父母在50岁以后血压均正常）。通过聚合酶链反应和用BseDI酶切进行基因分型，BseDI对268 bp的聚合酶链反应产物要么进行切割（C等位基因），要么不进行切割（T等位基因）。高血压组的T等位基因频率为0.43，而血压正常组为0.25（χ2 = 22；P = 0.00002；优势比 = 2.3；95%可信区间 = 1.7至3.3）。T等位基因与较高的治疗前血压相关：CC、CT和TT基因型的舒张压分别为105±7、109±16和128±28 mmHg（平均值±标准差）（单因素方差分析，P = 0.001）。携带T等位基因的女性高血压患者的血压高于男性高血压患者（方差分析，收缩压P = 0.006，舒张压P = 0.0003）。总之，本研究对一个有强烈家族病史的群体进行了研究，支持了G蛋白β3亚基基因的一种由基因决定的、具有生理活性的剪接变体在原发性高血压病因中起作用的观点。
