| Backgrounds and aimsStroke is the leading cause of disability and mortality in the Chinese population with hypertension. The risk factors of intracerebral hemorrhage, a subtype of stroke, more identified in Chinese than in western population, include hypertension, excessive drinking, anticoagulant and cerebral vascular malformation. Although cholesterol lowering treatment, such as statin, has been shown to lower the risk of ischemic stroke, it remains to determine whether the level of plasma high-density lipoprotein cholesterol has inverse association with intracerebral hemorrhage.The polymorphism of gene ATP2B1 has been demonstrated to be associated with hypertension in some genome-wide association studies in European, Korean, and Japanese. We hypothesized that the genetic variants could also change the risk of hard endpoints such as stroke, myocardial infarction or mortality.Materials and MethodsPlasma HDL-C was determined by using enzymatic methods and intracerebral hemorrhage was ascertained by using medical history, physical examination and brain imaging (computed tomography or MRI). A multivariable logistic regression model was used to calculate the odds ratios (OR) and 95% confidence interval (CI) of intracerebral hemorrhage according to the levels of plasma cholesterol.Our hypothesis was tested in a cohort of Chinese hypertensive population (n=1815). Single nucleotide polymorphism rs 12579302, a representative of Linkage Disequilibrium block covering 12 SNPs, was genotyped using MGB probe in ABI 7900 HT. The cohort was grouped based on participant's genotype and followed up for 3.5 years. The primary end-points are all types of stroke, fatal and non-fatal myocardial infarction and all cause-death.ResultsA total of 170 patients with intracerebral hemorrhage were identified from 6046 subjects. After adjustment for conventional cardiovascular risk factors, OR was 0.49 (95% CI 0.32 to 0.74, P=0.001) for the subjects in the third tertile of HDL-C (>1.65 mmol/L); 0.56 (95%CI 0.38 to 0.84, P=0.004) in the second tertile (1.38 to 1.64 mmol/L), as compared with the subjects in the first tertile (<1.38mmol/L). Subgroup analysis indicated that the protective effects of HDL-C from ICH were more significant in men as well as in lean subjects than in their correspondence controls, independent of hypertension.During the follow-up,86 subjects had stroke,17 had myocardial infarction and 33 dead of other causes. Cox regression was performed to adjust for the variables including age, gender, systolic blood pressure, hypercholesterolemia, diabetes mellitus, history of coronary heart disease, stroke at baseline. The results showed that the subjects with genotype rs 12579302 GG had lower risk of stroke (Relative Ratio 0.331,95% confidential interval 0.121-0.906), especially ischemic stroke (Relative Ratio 0.303,95% confidential interval 0.095-0.968), than those with the AA/AG carriers.ConclusionsOur results indicate that low plasma HDL-C (<1.38 mmol/L) may be associated with risk of intracerebral hemorrhage. The higher plasma high density lipoprotein cholesterol may be a protective factor for intracerebral hemorrhage.The common variant of gene ATP2B1 conferred protective effects on stroke risk in the Chinese hypertensive population and GG genotype confered the low risk of stroke, especially ischemic stroke compared with AA/AG genotype. BackgroundPolymorphism of ATP2B1 have been confirmed by several trials among European, Korean and Japnese population to associate with hypertension. The magnitude of lowered blood pressure level by different drug has been associted with the risk of clinical event in hypertension.AimsWe aimed to investigate whether polymorphism of ATP2B1 has any effect of antihypertensive drug on blood pressure.Material and MethodsA cohort of Chinese hypertensive patients were invited to our study which was divided into two groups according to the antihypertenvie treatment of nifidipine and captopril. The genotype of rs 12579302, which located in the promoter region of ATP2B1, was genotyped and blood pressure was followed up at 2 and 4 weeks during the antihypertensive treatment. The linear regression model adjustment for age, gender, baseline systolic blood pressure, hypercholestrolemia, diametes mellitus and coronary heart disease was calculated the effect of lowered level of blood pressure. The luciferase test was performed to determine the activity of promoter region of gene ATP2B1 with AA or GG genotype.ResultsThe level of systolic blood pressure after 4 weeks with captopril was lower in subjects with GG genotype of rs12579302 than in those with AA genotype (5.91mmHg,95% confidence interval 1.17-10.64, p=0.02) in linear regression model adjusting for age, gender, baseline systolic blood pressure, hypercholesterolemia, diabetes mellitus, coronary heart disease. No significant difference was found in the subjects with nifidipine between AA and GG genotype. The luciferase activity in GG genotype was half of those in A A genotype (p<0.001), even the same trend was seen after the stimulation of angiotensinâ…¡(p=0.009).Conclusion The response of systolic blood pressure in subjects with GG genotype of rs12579302 to captopril was better than those with AA genotype, suggesting that the antihypertensive effect of captopril may be associate with the variant of ATP2B1. |
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