Association Of Genetic Polymorphism In Tyrosine Hydroxylase Gene With Essential Hypertension In Hunan Han Population

Essential hypertension (EH) is a complex disease results from multiple minor genetic and environmental factors interact , and the genetic contribution to blood pressure (BP) level ranges from 30% to 60% . The catecholamines(CA), including dopamine, noradrenaline and adrenaline, play an important role in maintaining the homeostasis of cardiovascular system. Abnormal CA transmission is implicated in essential hypertension, plasma catecholamine is observed to be increased in the development of hypertension and noradrenaline is pivotal in the regulation of BP. Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme involved in the synthesis of catecholamines, by converting tyrosine into dopa , and plays important roles in the regulation of the central and sympathetic nervous system and cardiovascular function. These indicate that the TH gene plays an important role in the pathogenesis of hypertension in humans, therefore the TH gene is considered as a candidate for genetic susceptibility study of hypertension.Objective:To investigate the association of TH genetic polymorphism with EH susceptibility in Chinese Han of Hunan province by a case-control study.Methods: C-824T which is in the proximal promoter is selected to investigate the association between TH gene and essential hypertension susceptibility. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) is used to genotype the candidate Single Nucleotide Polymorphism(SNP). A case-control study is performed in 368 patients with essential hypertension and 353 normotensive controls of Han nationality recruited from Hunan province. Unconditinal logistic regression is performed to evaluate association of genotype with EH susceptibility after adjustment for risk factor.Results: 1. Genotype frequencies for TH gene C-824T (rs10770141) CC and CT+TT genotypes were 89.9% and 10.1% in cases, respectively, 88.7% and 11.3% in controls. No significant difference was observed for genotype distribution of C-824T polymorphism between the cases and controls(χ~2=0.308, P=0.579). Allele frequencies of TH gene C-824T also showed no significant difference between the cases and controls(χ~2=0.425,P=0.515). 2. When adjusted by EH risk factors including sex, age, body mass index( BM), smoking, alcohol drinking, EH history in the first degree relatives, serum creatinine, blood sugar, triglyeride, cholesterol, high density lipoprotein(HDL) and low density lipoprotein(LDL), results of unconditional logistic regression analysis showed that there was no relationship between TH C-824T polymorphism and EH susceptibility (P=0.264, OR=0.723, 95%CI=0.409~1.278). 3. When stratified by gender, no significant difference in genotype distribution of TH C-824T polymorphism was observed between the cases and controls in either male or female (P=0.841 and P=0.288). 4. In controls, diastolic blood pressure(DBP) in individuals with CT+TT genotype (81±8 mmHg) was higher than CC genotype (77±9 mmHg, P=0.015) of TH C-824T polymorphism. When stratified by gender, there was significant difference in DBP between CT+TT genotype and CC genotype in male(P = 0.018), but not in female (P=0.083) in controls.Conclusion: 1. There is no relationship between TH gene C-824T polymorphism and EH susceptibility in Hunan Han population; 2. The TH gene C-824T polymorphism is possibly associated with DBP in male Hunan Han population.