ACE Gene I/D Polymorphism and Sarcoidosis Pulmonary Disease Severity

Abstract

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.

Association between I/D polymorphism in the ACE gene and sarcoidosis in Turkish patients

“…In the same ethnic group, disease risk was found to significantly increase with the DD genotype in patients with positive family history (Maliarik et al 1998). In a study on British and Czechoslovakian patients diagnosed with sarcoidosis, McGrath et al examined the correlation between the ACE genotype and disease sensitivity, severity, and progression, but they did not observe significant association (McGrath et al 2001). Consistent with the results of our study, Hatemi et al (Furuya et al 1996).…”

“…Along with the detection of familial sarcoidosis, research on genetic predisposition to sarcoidosis has gained momentum (Fite et al 1998;Rybicki et al 1996;Sverrild et al 2008). However, contradictory results were obtained using different ethnic groups; therefore, further studies are required to test whether the ACE genotype is linked to sarcoidosis predisposition (Maliarik et al 1998;McGrath et al 2001;Alia et al 2005;Kruit et al 2010;Schurmann et al 2001;Hatemi et al 2001). The objectives of our study were to determine the distribution of I/D polymorphism in the ACE gene in Turkish patients as a distinct ethnic group and to investigate whether such polymorphism is associated with a predisposition to sarcoidosis.…”

PET/CT findings in sarcoidosis: Analysis of 53 cases

“…Sarkoid granülomlar tarafından üretilen ACE'nin aktivite tayini ve tedavi planlamada kullanılmış, ancak kronik sarkoidozlu hastaların yalnızca %60'ında ACE normalin üstünde saptanmış ve hastalığın ciddiyeti, progresyonu, ve tedavi yanıtı ile ilişkili olmadığı gösterilmiştir 9,10 . Hastalarımızın ortalama ACE düzeyi 52.3 U/L saptanmıştır.…”

Sarcoidosis and granuloma genes: a family-based study in African-Americans

“…Conflicting case-control study results with respect to sarcoidosis risk exist for polymorphisms in the ACE [7][8][9][10][11][12][36][37][38][39][40], VDR [27,41], and TNF-a [17][18][19][20]42] genes (table 5). Therefore, the current authors tested polymorphisms in these genes for associations with sarcoidosis in African-American families.…”

“…The ACE D allele, which is associated with higher serum ACE levels [6], has been found associated with increased sarcoidosis risk in African Americans [8], Japanese women [7] and in sarcoid-affected family members from a German population [9]. Conversely, other studies in both Caucasians [10,11] and Japanese [12] have failed to find an association between the ACE I/D polymorphism and sarcoidosis susceptibility or progression.…”