Deletion Allele of Angiotensin-Converting Enzyme Gene Increases Risk of Essential Hypertension in Japanese Men

Higaki, Jitsuo; Baba, Shunroku; Katsuya, Tomohiro; Sato, Noriyuki; Ishikawa, Kazuhiko; Mannami, T.; Ogata, Jun; Ogihara, Toshio

doi:10.1161/01.cir.101.17.2060

Cited by 200 publications

(147 citation statements)

References 18 publications

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“…In line with gender‐specific differences in the effect of the ACE‐I/D polymorphism in various conditions and/or diseases, such as blood pressure (among healthy individuals) (Avila‐Vanzzini et al., 2015), hypertension (Higaki et al., 2000; Sipahi, Budak, Şen, Ay1, & Şener, 2006), schizophrenia (Mazaheri, 2015; Nadalin, Buretić‐Tomljanović, Ristić, Jonovska, & Tomljanović, 2015; Nadalin et al., 2012), as well as MS (Lovrečić et al., 2006), and according to observations of gender–gene interaction in risk for nicotine dependence in general population (Beuten, Payne, Ma, & Li, 2006; Beuten et al., 2005; Nedic et al., 2010; Tochigi et al., 2007) and specific diseases (i.e., schizophrenia) (Nadalin, Buretić‐Tomljanović, Rebić, Pleša, & Šendula Jengić, 2016) association analyses between ACE‐I/D polymorphism and smoking habits were performed separately among male and female patients. Furthermore, there is also evidence that estrogen may influence dopaminergic neurotransmission, since it has been observed that estrogen treatment reduces dopamine receptor D2 levels in several rat brain regions (Chavez et al., 2010).…”

Section: Resultsmentioning

confidence: 99%

The lack of association between angiotensin‐converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis

et al. 2016

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ObjectiveBlood‐borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin‐converting enzyme (ACE), an enzymatic cascade known as the renin–angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE‐I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE‐I/D polymorphism might influence smoking behavior among patients with MS.Patients and MethodsGenotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction.ResultsWe revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE‐I/D polymorphism and either pack‐year smoking history or number of cigarettes smoked daily (p > .05, respectively).ConclusionThe ACE‐I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE‐I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.

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Section: Resultsmentioning

confidence: 99%

The lack of association between angiotensin‐converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis

et al. 2016

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“…33 On the other hand, the frequency of the 825T allele in our population was much lower than that in Africans (79%), whereas it was slightly higher than the southern Chinese population (43.2%) reported by Siffert et al 37 As for the ACE I/D polymorphism, the D allele of the ACE gene is reportedly associated with the development of EH. 15 Many studies have examined possible associations between the ACE I/D poly- 18 By contrast, Zaman et al 13 and Matsubara et al 15 reported that there were no associations between the ACE I/D polymorphism and hypertension in males or females. Our present findings also showed no significant gender-specific associations.…”

Section: Discussionmentioning

confidence: 99%

“…16,17 Several studies have demonstrated significant age-related associations between ACE I/D polymorphisms and hypertension in gender-specific analyses among different populations, among whom there is association and genetic linkage of the ACE I/D polymorphism with hypertension for males but not for females. 9,18 The DD genotypes were less common in elderly hypertensive Caucasians than in age-matched normotensive subjects. 19 Heterotrimeric guanine nucleotide-binding proteins (G proteins) are expressed in all human cells.…”

Section: Introductionmentioning

confidence: 92%

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

et al. 2006

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Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene-gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. The G-protein b3-subunit (GNB3) 825T allele, associated with enhanced G-protein signalling, is a strong candidate for interactions with polymorphisms, such as insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme (ACE) gene. We investigated whether there is an association between GNB3 C825T and ACE I/D polymorphisms for the development of EH. We carried out a case-control study of 688 hypertensive and 924 normotensive subjects recruited from South Korea. The GNB3 C825T and ACE I/D genotypes were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associated with hypertensive status in either males or females. Logistic regression analysis indicated that the GNB3 825T allele carriers were positively associated with EH in males (odds ratio (OR) for TT/CT, 1.459; 95% confidence interval (CI), 1.048-2.033, P ¼ 0.0255). In analysis of gene-gene interaction, we found that there was a significant interaction between the GNB3 825T and ACE D alleles (Po0.05). OR for EH was significantly higher in 825T allele carriers with ACE D allele (OR, 1.490; 95% CI, 1.117-1.987, P ¼ 0.0067). A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.

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“…6 Several studies reported evidence of a significant relation between the ACE I/ D polymorphism and hypertension in male subjects but not in female subjects. [7][8][9] However, it was also shown that this relation was not consistently seen in male subjects, but was changeable depending on other factors such as age. 10 In addition, recent studies of population-based samples of three differ-ent areas in Japan presented conflicting results regarding the association of the ACE I/D polymorphism and hypertension.…”

Section: Introductionmentioning

confidence: 98%

“…10 In addition, recent studies of population-based samples of three differ-ent areas in Japan presented conflicting results regarding the association of the ACE I/D polymorphism and hypertension. 9,11,12 We, thus, performed the present study to determine the relation between the ACE I/D polymorphism and blood pressure (BP), or frequency of hypertension, respectively, in Japanese male subjects who participated in the health checkup programme of our hospital.…”

Section: Introductionmentioning

confidence: 99%

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects

et al. 2003

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Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investigated the relation between the ACE I/D polymorphism and blood pressure (BP), or the frequency of hypertension, respectively, in 706 Japanese male subjects who participated in the health check-up programme of our hospital. The ACE I/D polymorphism was determined by the polymerase chain reaction technique. Of 706 subjects, 203 were found to have hypertension and the other 503 were found to be normotensive. In all subjects, the frequencies of the DD, ID, and II genotypes were 0.123, 0.432, and 0.445, respectively, and the allelic frequency of the D allele was 0.339. In the younger subjects aged o50 years (n ¼ 264), neither systolic nor diastolic BP differed significantly among the genotypes. Conversely, in the older subjects agedX50 years (n ¼ 442), the systolic BP was significantly higher by 5.9 mmHg in the subjects with the ID genotype than those with the II genotype (Po0.01), and the diastolic BP was significantly higher in the subjects with the DD and ID genotypes by 5.1 and 3.3 mmHg, respectively than those with the II genotype (Po0.05 for each), although age, BMI, percentage of smoking habits, drinking habits, or the use of antihypertensive drugs did not differ significantly among the genotypes. In addition, in the older subjects, the hypertensive subjects showed significantly higher frequencies of the DD and ID genotypes and the D allele than the normotensive subjects. These results demonstrated that there was no significant association of the ACE I/D polymorphism with BP or a prevalence of hypertension in younger Japanese men aged o50 years but there was in older Japanese men aged X50 years.

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Deletion Allele of Angiotensin-Converting Enzyme Gene Increases Risk of Essential Hypertension in Japanese Men

Abstract: Despite the lower frequency of the DD genotype in Japanese than in whites, the ACE gene polymorphism was associated with increased risk for hypertension, suggesting that this polymorphism is a mild but certain genetic risk factor for essential hypertension in men.

Cited by 200 publications

References 18 publications

The lack of association between angiotensin‐converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis

The lack of association between angiotensin‐converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects

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