Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: An observation based on arsenic-exposed individuals

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• 作者：Meei-Maan  ; Wu^a ;   ; ^b ;   ; ^{mmwu@tmu.edu.tw} ; Hung-Yi  ; Chiou^a ; Chi-Ling  ; Chen^c ; Ling-I  ; Hsu^d ; Li-Ming  ; Lien^e ; Chih-Hao  ; Wang^f ; Yi-Chen  ; Hsieh^a ; Yuan-Hung  ; Wang^a ; Yu-Mei  ; Hsueh^a ;   ; ^g ; Te-Chang  ; Lee^h ; Wen-Fang  ; Cheng^b ; Chien-Jen  ; Chen^d ;   ; ⁱ
• 关键词：Blood pressure ; Heme oxygenase-1 ; Genetic polymorphism ; Cardiovascular mortality ; Risk factors ; Population study
• 刊名：Atherosclerosis
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：219
• 期：2
• 页码：704-708
• 全文大小：111 K

文摘

Objective

Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts.

Methods

Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or L (?7 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates.

Results

Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles.

Conclusions

HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors.