The Effects Of GNB3 And ENOS Genes Polymorphism And Related Environmental Factors On Hypertension And Stroke

Objective The pathogenesis of essential hypertension (EH) is not fully understood as yet. Now it is accepted that EH is associated with the interaction between gene and environmental factors. EH is the major risk agent to strok. It is important to explore the genetic mutation and environmental risk factors in hypertension. G protein is linked to activation of adenyl cyclase (AC) which involve in signal transduction between receptor and effector. A polymorphism at position 825 (C-T) of the gene that encodes the G protein 133 subunit (GNB3) was recently shown to be associated with human EH. Nitric oxide (NO) synthesized by endothelial NO synthase (eNOS) vasodilates by activating guanylate cyclase (GC). It was reported a polymorphism located in exon 7 (G894T) of eNOS gene related to alteration in vascular function of EH.ethods To investigate whether these two polymorphisms binding other risk factors are associated with EH and stroke, we analyzed the GNB3 and eNOS gene variant and some enviromental factors in 112 patients with EH, 72 patients with stroke and matched controls. The diagnosis of EH was according to 1999 WHO/ISH criterion and stroke to 1997 MONICA of WHO. Questionnaire refered to life style, dietary, smoking, alcohol consumption, psychological and mental state, economy, body mass index, waistline, etc. Genotypes of the polymorphisms were determined by polymerase chain reaction (PCR), the PCR products digested by restriction endonuclease (Ban IK BseDI).Results Genotype distribution for the GNB3 C825T genotype wassignificantly different between patients with EH or stroke (CC=0.34, CT=0.53, TT=0.13; CC=0.32, CT=0.58, TT=0.10 respectively)and controls (CC=0.59, CT=0.36, TT=0.05, x 2=6.9, P<0.05; CC=0.65, CT=0.32, TT=0.03, x 2=14.6, P<0.01), but not between stroke groups with or without EH. and the 825T allele was associated with higher risk disposing EH or stroke (OR=2.2, 95%CI 1.1 to 4.6; OR=0.3, 95%CI 0.1 to 0.6 respectively). There was not significantly different in genotype distribution for the eNOS gene G894T genotype between patient groups and controls, but there was among some related risk factors, such as salt intake, snored and waist-to-hip ratio (WHR) etc. Logistic regression analysis showed that GNB3 C825T polymorphism and WHR were closely associated with EH and stroke.Conclusion 1)GNB3 825T allele is a risk factor to EH and stroke, 2)the effect of GNB3 825T allele on stroke is not completely through EH, 3)the polymorphism of eNOS gene G894T binding some other risk factors play an role in the pathogenesis of EH and stroke, 4)salt intake, excitation disposition, snoring, increased WHR are risk factors to EH. Systolic blood pressure (SBP), alcohol consumption, increased WHR, snoring etc are risk factors to stroke. The polymorphism of eNOS gene G894T may take effect partially through these factors.