Angiotensinconverting enzyme gene polymorphism in

Authors: Adel M AlAwadhi Eman A Hasan Prem N Sharma M Zafaryab Haider Khaled AlSaeid

Publish Date: 2007/04/14

Volume: 27, Issue: 12, Pages: 1119-

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Abstract

To investigate the frequency of angiotensinconverting enzyme ACE gene insertion/deletion I/D polymorphism genotypes in adults with psoriatic arthritis PsA a heterogeneous chronic disease with autoimmune pathology ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanism The frequency of ACE gene I/D polymorphism genotypes was determined in 51 adults with PsA from Kuwait and compared to that in 100 ethnically matched healthy controls using polymerase chain reaction The distribution of ACE I/D polymorphism and allele frequencies in PsA patients were not significantly different from controls P  005 Further analyses of PsA patients showed that ACE I/D gene polymorphism was not associated with family history clinical manifestations and disease severity However the frequency of II genotype was significantly higher in patients with late disease onset than in those with early onset 25 vs 3 P = 004 No difference was found between the distribution of the ACE genotype in PsA patients and the general population in Kuwait However the presence of II genotype may confer susceptibility to the development of late onset PsAPsoriatic arthritis PsA is a chronic systemic inflammatory arthritis disorder characterized by joint inflammation that is associated with cutaneous psoriasis PsA is relatively common affecting approximately 1 of the population 1 Although previously considered to be a relatively mild form of arthritis there has been a growing appreciation that PsA can be progressive destructive and deforming PsA can have profound deleterious effects to an extent comparable to those of other pernicious chronic conditions such as rheumatoid arthritis RA 2 3 The exact cause of psoriasis and its associated arthritis is not yet known It seems likely however that genetic immunologic and environmental factors all may contribute 4 It also seems reasonable to postulate that the skin and joint disease have a similar pathogenesis although the activity of these manifestations does not always change in parallel Genetic association with PsA has been most extensively studied in human leukocyte antigen HLA class I and II polymorphism 5 6 7 8 immunoglobulin genes 9 CARD15 gene 10 tumor necrosis factor TNF genes 11 12 and SEEK I gene 13The Angiotensinconverting enzyme ACE gene is located on the long arm of chromosome 17 14 and contains an insertion I and deletion D polymorphism within intron 16 of the presence or absence of a 287 bp repeat sequence Of the three possible genotypes DD and II homozygotes and ID heterozygotes the carriers of DD genotype have the highest levels of serum ACE while those with the II genotype have the lowest serum levels 15ACE is expressed in a wide range of tissues including skin vascular endothelium and immune cells 16 17 18 Almost half of the patients with psoriasis have been found to have an elevated serum ACE activity 19 ACE activates Angiotensin I into Angiotensin II inactivates bradykinin via the kallikrein–kininogen system and plays a major role in the rennin–angiotensin system RAS It is suggested that inhibition of bradykinin degradation by ACE inhibitors alters the kinin–kallikrein arachidonic acid system leading to increased concentrations of kinins and related inflammatory metabolites in the skin which might contribute to inflammatory skin lesions in psoriasisThere was only one report in literature denoting the presence of Iallele might confer susceptibility to development of psoriasis in individuals from psoriatic families 20 but none on PsA Therefore the present study was undertaken to evaluate the possible role of I/D polymorphism of the ACE gene in the etiopathogenesis of PsA

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