Angiotensin I-Converting Enzyme Gene Polymorphism Is Associated With Myocardial Infarction, but Not With Retinopathy or Nephropathy, in NIDDM

Fujisawa, Tomomi; Inoue, Hiroshi; Shen, Gong-Qing; Yamato, Eiji; Takekawa, K.; Nakagawa, Yusuke; Hamada, Y.; Ueda, Hironori; Rakugi, Hiromi; Higaki, Jitsuo; Ohishi, Mitsuru; Fujii, Kenshi; Fukuda, Masakatsu; Ogihara, Toshio

doi:10.2337/diacare.18.7.983

Cited by 96 publications

(46 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, we detected no association between the AT1R polymorphism and CVD events; however, the AGT polymorphism appeared to have an influence on the incidence of cardiovascular diseases in a Kaplan-Meier analysis. In cross-sectional studies, the ACE DD genotype has functioned as a risk factor for CVD in Japan; 10,[19][20][21][22]23 we confirmed this risk in our cohort. Subjects with the DD genotype exhibited higher tissue ACE activity and increased ACE expression in the plaque of acute coronary syndrome, observations that may explain why hypertensive patients with the DD genotype have a higher incidence of cardiovascular disease.…”

Section: Discussionsupporting

confidence: 81%

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

et al. 2011

Self Cite

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) adversely affects stroke and cardiovascular disease; polymorphisms in genes involved in this system are associated with cardiovascular disease. The aim of the present study was to confirm the genetic risk of these polymorphisms for stroke and cardiovascular events in a cohort study of 515 hypertensive patients in Japan (follow-up period 90.6±30.2 months). The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE), the M235T amino acid change in angiotensinogen, and the A1166C polymorphism in angiotensin II type 1 receptor were determined by TaqMan PCR. In Kaplan-Meier analyses, the ACE I/D polymorphism was a risk factor for cerebro-cardiovascular events, especially cardiovascular events (Po0.0001), and the M235T mutation was a risk factor for cardiovascular events (Po0.0105). The cumulative rates of cerebro-cardiovascular end points for the ACE polymorphism were 10.6, 16.4 and 42.2% for the II (n¼207), ID (n¼244) and DD (n¼64) genotype carriers, respectively (Po0.0001). Cox's proportional hazard models revealed that the ACE DD genotype was a risk factor for cerebro-cardiovascular and cardiovascular events (after adjusting for common risk factors), anti-hypertensive treatment and RAS inhibition (Po0.0001). Moreover, after adjustment for the common risk factors left ventricular hypertrophy and previous myocardial infarction/stroke, these phenomena were preserved. Thus, the DD genotype of ACE may be a genetic risk factor for cerebro-cardiovascular disease, especially cardiovascular events, in hypertensive patients in Japan.

show abstract

Section: Discussionsupporting

confidence: 81%

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…The D allele frequency was 40.2 and 32.8% in the case and the control groups, respectively, which is in line with previous reports of 29.3-41.6% frequencies in other Asian populations (5,10,11,13) and is much lower than the 52-57% frequencies reported in Caucasian populations (12,14,15). The observed genotype distribution was in Hardy-Weinberg equilibrium in control subjects ( 2 1 ϭ 0.03, P ϭ 0.96) and was marginally deviated from the equilibrium in case subjects ( 2 1 ϭ 3.77, P ϭ 0.05).…”

supporting

confidence: 92%

“…ACE, a key enzyme in the renin-agiotensin system, catalyzes the conversion of angiotensin I to angiotensin II in liver and inactivates bradykinin in many tissues. ACE insertion/deletion (I/D) polymorphism, characterized by the presence (insertion) or absence (deletion) of a 287-bp AluI-repeat sequence inside intron 16, has been suggested to be associated with coronary heart disease and nephropathy in type 2 diabetic patients (3)(4)(5)(6)(7)(8)(9). Association studies of ACE I/D polymorphism and type 2 diabetes in various populations have yielded conflicting results (10 -13).…”

mentioning

confidence: 99%

Insertion/Deletion Polymorphism of the ACE Gene Is Associated With Type 2 Diabetes

Feng

Niu

et al. 2002

Diabetes

View full text Add to dashboard Cite

In an attempt to examine the role of an ACE gene insertion/deletion (I/D) polymorphism in type 2 diabetes, we conducted a case-control association study among 132 couple-pairs from northern China. The genotype frequencies for II, ID, and DD were 39.8, 39.8, and 20.3%, respectively, in the case group and 44.8, 44.8, and 10.4% in the control group. The DD frequency was significantly higher in the case group than in the control group ( 2 1 ‫؍‬ 4.77, P ‫؍‬ 0.03), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study population. Diabetes 51: 1986 -1988, 2002 T ype 2 diabetes is a complex disorder accounting for ϳ90 -95% of all diabetes syndromes. Despite numerous reports suggesting a substantial genetic contribution to the susceptibility of type 2 diabetes, no major susceptibility genes have been identified so far (1, 2). ACE, a key enzyme in the renin-agiotensin system, catalyzes the conversion of angiotensin I to angiotensin II in liver and inactivates bradykinin in many tissues. ACE insertion/deletion (I/D) polymorphism, characterized by the presence (insertion) or absence (deletion) of a 287-bp AluI-repeat sequence inside intron 16, has been suggested to be associated with coronary heart disease and nephropathy in type 2 diabetic patients (3-9). Association studies of ACE I/D polymorphism and type 2 diabetes in various populations have yielded conflicting results (10 -13). Here, we report a case-control association study of ACE I/D polymorphism and type 2 diabetes in a Chinese population.We tested the relationship between ACE I/D polymorphism and type 2 diabetes in 132 Chinese spousal casecontrol pairs, each pair consisting of a type 2 diabetes proband and his/her nondiabetic spouse. Every proband met the World Health Organization criteria for type 2 diabetes and had at least one first-degree family relative (parent or sibling) with type 2 diabetes. Each nondiabetic spouse control had to be free from any family history of type 2 diabetes and had to have normal glucose tolerance during a 75-g oral glucose tolerance test (OGTT). The phenotypic characteristics of the diabetic and spousal control subjects are summarized in Table 1. Age and sex were well matched between the case and the control groups, whereas the average BMI, waist-to-hip ratio, blood pressure, and serum concentrations of insulin, C-peptide, total cholesterol, and triglycerides were significantly higher in the case subjects. The genotype frequencies of ACE gene I/D polymorphism were shown in Table 2.The D allele frequency was 40.2 and 32.8% in the case and the control groups, respectively, which is in line with previous reports of 29.3-41.6% frequencies in other Asian populations (5,10,11,13) and is much lower than the 52-57% frequencies reported in Caucasian populations (12,14,15). The observed genotype distribution was in Hardy-Weinberg equilibrium in control subjects ( 2 1 ϭ 0.03, P ϭ 0.96) and was marginally deviated from the equilibrium in case subjects ( 2 1 ϭ 3.77, P ϭ 0.05). A signif...

show abstract

“…These include the nitric oxide synthases (NOS) that mediate vasodilation and the endothelins (ETs) that are vasoconstrictors. Angiotensin-converting enzyme (ACE), which converts angiotensinogen to angiotensin, is another important mediator of vasoconstriction and homeostasis; however, studies to date on genetic markers of members [48][49][50][51][52][53][54][55][56] of this signalling pathway have not shown definitive evidence of direct genetic risk (see Table 1). …”

Section: Mhc and Immunity Markersmentioning

confidence: 99%

Molecular genetics of microvascular disease in diabetic retinopathy

Warpeha

Chakravarthy

2003

Eye

View full text Add to dashboard Cite

Angiotensin I-Converting Enzyme Gene Polymorphism Is Associated With Myocardial Infarction, but Not With Retinopathy or Nephropathy, in NIDDM

Abstract: These data indicate that ACE gene polymorphism is associated with MI, but not with retinopathy or nephropathy, in patients with NIDDM and suggest that the ACE gene confers susceptibility to diabetic macroangiopathy but not to microangiopathy.

Cited by 96 publications

References 7 publications

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

Insertion/Deletion Polymorphism of the ACE Gene Is Associated With Type 2 Diabetes

Molecular genetics of microvascular disease in diabetic retinopathy

Contact Info

Product

Resources

About