Angiotensin-converting enzyme gene polymorphism and risk of sarcoidosis.
The angiotensin-converting enzyme (ACE) has been implicated in the pathophysiology of sarcoidosis. Serum ACE levels in normal and sarcoidosis patients are influenced by an insertion (I)/deletion (D) polymorphism in the ACE gene. To elucidate the role of this ACE gene polymorphism in sarcoidosis, we conducted a case-control study in African Americans and Caucasians. The ACE gene (I/D) polymorphism did not differ between 60 Caucasian cases and 48 control subjects (p = 0.577). In contrast, a comparison of 183 African-American cases and 111 control subjects resulted in a marked difference in genotypic distributions (p = 0.005). In African Americans, the risk for sarcoidosis was 1.30 (95% confidence interval [CI] = 0.72 to 2. 36) for ID heterozygotes, and 3.17 (95% CI = 1.50 to 6.71) for deletion/deletion (DD) homozygotes. The risk associated with the DD homozygotes was even greater in African Americans when cases were restricted to those with a positive family history (odds ratio = 4. 83; 95% CI = 1.86 to 12.59). Further analyses of African-American cases showed that the ACE genotype was not associated with disease severity, extrathoracic involvement, or overall radiographic change 2 to 4 yr after diagnosis. We did find a moderate association between the II genotype and radiographic progression (OR = 2.97; 95% CI = 1.01 to 8.76). Our results suggest the ACE genotype may play a more important role in sarcoidosis susceptibility and progression in African Americans than Caucasians.
Maliarik
M J
MJ
Division of Pulmonary and Critical Care Medicine and Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan, USA.
Rybicki
B A
BA
Malvitz
E
E
Sheffer
R G
RG
Major
M
M
Popovich
J
J
Iannuzzi
M C
MC
D000328:Adult; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012507:Sarcoidosis / Q000097:blood / Q000145:classification / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
D007703:Peptidyl-Dipeptidase A