Influence of angiotensin-converting enzyme gene insertion/deletion polymorphism on rheumatic valve involvement, valve severity and subsequent valve calcification.
OBJECTIVE
The relationship between the severity of chronic rheumatic heart disease (RHD) and predisposing factors is unknown, and genetic predictors for severe scarring and calcification of the mitral valve are not well defined. A high angiotensin-converting enzyme (ACE) activity has been demonstrated in valve tissue. Thus, a case-control study was conducted to investigate any possible relationship between ACE gene polymorphisms and chronic mitral valve disease severity and calcification.


METHODS
This case-control study included 82 patients (24 males, 58 females; mean age 40.3 +/- 14.7 years) with chronic rheumatic mitral valve, and 154 control subjects (53 males, 101 females; mean age 43.4 +/- 13.4 years). ACE gene insertion/deletion (I/D) polymorphisms were identified using polymerase chain reaction methods.


RESULTS
Among RHD subjects, 31 (30.6%) were D/D, 25 (32.7%) were I/D, and 26 (18.8%) were I/I. Among controls, 57 (57.4%) were D/D, 69 (61.3%) were I/D, and 28 (35.2%) were I/I. The frequency of ACE I/I genotype was higher in RHD subjects than in controls (chi2 = 7.4, df = 2, p < 0.030; D/D versus I/D versus I/I), or (chi2 = 5.5, df = 1, p < 0.019; DD + ID versus II). Predisposition to RHD was significantly less frequent in the D/D genotype. There was no statistically significant difference in the genetic analysis of RHD with respect to mitral valve score, severity of mitral regurgitation and left atrial diameter. Mitral valve calcification was significantly associated with a higher frequency of I/I genotype and I/D genotype than D/D genotype alone (chi2 = 6.2, df = 2, p = 0.043). The ACE I/I genotype was associated with a predisposition to a greater risk of severe calcific valve disease.


CONCLUSIONS
The ACE I/I genotype is more common in patients with rheumatic valve disease than in the normal population. This suggests that the ACE gene polymorphism may be involved in the pathogenesis of rheumatic heart disease.
Davutoglu
Vedat
V
Department of Cardiology, University of Gaziantep, School of Medicine, Sahinbey Medical Center, Gaziantep, Turkey. davutoglu@gantep.edu.tr
Nacak
Muradiye
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001022:Aortic Valve Insufficiency / Q000201:enzymology / Q000235:genetics; D002114:Calcinosis / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D004251:DNA Transposable Elements / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000201:enzymology* / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012214:Rheumatic Heart Disease / Q000201:enzymology* / Q000235:genetics; D014262:Tricuspid Valve Insufficiency / Q000201:enzymology / Q000235:genetics
D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A