Angiotensin-converting enzyme (ACE) I/D gene polymorphism in multiple sclerosis

Background and goals: Increased angiotensin-converting enzyme (ACE) activity in the blood and cerebrospinal fluid of MS patients and the suppression of disease development in experimental autoimmune encephalomyelitis after ACE blockade suggest that ACE may play a role in the pathogenesis of MS. Serum levels of ACE are modulated by an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene. The aim of this study was to investigate the possible influence of the ACE I/D polymorphism on MS susceptibility in Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian populations that share the same geographic location and have a similar ethnic background of Slavic origin. Materials and Methods: The study included a total of 867 patients (588 female, 279 male) who fulfilled McDonald’s criteria for MS. The control group consisted of 851 healthy, unrelated, ethnically matched blood donors who had no family history of MS or any other inflammatory-demyelinating disease. The ACE I/D polymorphism was genotyped by polymerase chain reaction. Results: Allele and genotype frequencies of pooled MS patients and controls were not significantly different (P > 0.05). When MS patients were stratified by gender and disease course, no significant differences (P > 0.05) in genotype distribution were observed. Meta-analysis revealed that the ACE DD genotype does not increase the risk for MS (OR = 1.08, 95% CI 0.88 – 1.33, z = 0.741, P = 0.459, Pheterogeneity = 0.814). Conclusion: Our results indicate that the ACE I/D polymorphism overall does not contribute to MS susceptibility in the Slavic populations investigated.