Association Between Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and Risk of Rheumatic Heart Disease

Abstract

SUMMARYScarring and collagen deposition in the valves and destruction of myocytes may result from the combined effects of a smoldering rheumatic process and a constant trauma to the mitral valve or aortic valve by the turbulent flow in rheumatic heart disease (RHD). It has been suggested that angiotensin I-converting enzyme (ACE) may be responsible for the increased valvular fibrosis and calcification in the pathogenesis of RHD. However, the role of ACE genetic variant in RHD has not been studied among the Chinese population in Taiwan. Hence, a case-controlled study was carried out to investigate the possible relationship between the ACE gene insertion/deletion (I/D) and G2350A polymorphisms and RHD.A group of 115 patients with RHD documented by echocardiography and 100 ageand sex-matched normal control subjects were studied. ACE gene I/D and G2350A polymorphisms were identified by polymerase chain reaction-based restriction analysis.There was a significant difference in the distribution of ACE I/D genotypes (P = 0.02) and allelic frequencies (P = 0.04) between RHD cases and normal controls. An odds ratio for the risk of RHD associated with the ACE I/D II genotype was 2.12 (95% CI, 1.21-3.71). An odds ratio for the risk of RHD associated with the ACE I allele was 1.50 (95% CI, 1.02-2.21). The ACE G2350A polymorphism showed no association with RHD (P = 0.90). Further categorization of RHD patients into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these gene polymorphisms when compared between the two subgroups.This study shows that patients with RHD have a higher frequency of ACE II genotype and I allele, which supports a role for ACE I/D gene polymorphisms in determining the risk of RHD in Taiwan Chinese. (Jpn Heart J 2004; 45: 949-957)

Lack of Association of Genetic Polymorphisms in the Interleukin-1 .BETA., Interleukin-1 Receptor Antagonist, Interleukin-4, and Interleukin-10 Genes With Risk of Rheumatic Heart Disease in Taiwan Chinese

“…The difference might be caused by ethnic factors. 17) We also found that patients with RHD had a lower frequency of transforming growth factor-β1 (TGF-β1) C-509T CC genotype and a higher frequency of T869C T allele, which supported a role for the TGF-β1 gene C-509T and T869C polymorphisms in determining the risk of RHD in Taiwan Chinese. 18) A population-based analysis of unrelated individuals with IL-1β TaqI polymorphism showed an association between this polymorphism and IL-1β secretion after lipopolysaccharide stimulation studied by analyzing the in vitro stimulated monocyte IL-1β response.…”

Angiotensin-converting enzyme gene insertion/deletion polymorphism in Saudi patients with rheumatic heart disease

“…With respect to Arab populations, only a single study from Egypt has reported an association between the DD genotype and RHD. 12 Two studies from Turkey 10 and Taiwan 9 have reported an association with the II genotype. This inconsistency may be due to ethnic factors, since the distribution of the ACE I/D polymorphism is known to be different between various ethnic populations.…”

“… 11 However, no significant differences in the distribution of the I/D polymorphism between MVD and CVD subgroups have been observed in the Egyptian and Taiwanese populations. 9 , 12 It is important to note that in patients with RHD, the cardiac lesions may progress over time to involve more valves and the condition develops from MVL to CVL.…”

“… 8 The ACE I/D polymorphism has been associated with an increased risk of RHD in different populations. 9 - 11 With respect to Arab populations, only one study from Egypt has reported that the ACE DD genotype is associated with an increased risk of RHD. 12 Since there is a lack of data regarding the role of this polymorphism in the Saudi population, we evaluated the ACE I/D polymorphism in Saudi patients with RHD.…”

Some of the People, Some of the Time

“…111,112 These polymorphisms are strongly associated with valvular damage compared with individuals with previous ARF but normal valves. 113 …”