title: 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.
authors.affiliation: "Vinča" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia. Electronic address: majaz@vinca.rs.
authors.forename: Maja
authors.initials: M
authors.lastname: Živković
authors.affiliation: "Vinča" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Kolaković
authors.affiliation: "Vinča" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Stojković
authors.affiliation: Military Medical Academy, Clinic for Neurology, Belgrade, Serbia.
authors.forename: Evica
authors.initials: E
authors.lastname: Dinčić
authors.affiliation: Military Medical Academy, Clinic for Neurology, Belgrade, Serbia.
authors.forename: Smiljana
authors.initials: S
authors.lastname: Kostić
authors.affiliation: "Vinča" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Alavantić
authors.affiliation: "Vinča" Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanković
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors; D055771:Serbia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
keywords: Gene; Multiple sclerosis; Polymorphism; Renin-angiotensin system