Renin-angiotensin system gene polymorphisms as risk factors for multiple sclerosis

Abstract

The components of renin-angiotensin system, such as angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II receptor type 1 and 2 (AT1R and AT2R), are expressed in the central nervous system and leukocytes and proposed to be involved in the inflammation and pathogenesis of multiple sclerosis (MS). ACE I/D, AT1R 1166A/C and AT2R -1332A/G are functional polymorphisms associated with phenotypes of diverse chronic inflammatory diseases. The aim of this study was to investigate the association between ACE I/D, AT1R 1166A/C and AT2R -1332A/G gene polymorphisms and MS in Serbian population. A total of 470 MS patients and 478 controls participated in the study. Allele-specific polymerase chain reaction (PCR) was performed for genotyping of the ACE polymorphism. The AT1R and AT2R genotyping was done by duplex PCR and restriction fragment length polymorphism analysis. Both ACE homozygotes, II and DD, were significantly overrepresented in MS patients, compared to controls (χ(2) test p=0.03). Neither genotype nor allele frequencies of AT1R 1166A/C polymorphism were significantly different between patients and controls. Significant overrepresentation of AT2R -1332 AA genotype in female patients, compared to female controls, was detected (OR=1.67, 95%CI=1.13-2.49, χ(2) test p=0.01), suggesting that this genotype could be a gender-specific genetic risk factor for MS.

Keywords: Gene; Multiple sclerosis; Polymorphism; Renin-angiotensin system.