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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Angiotensin-converting enzyme insertion/deletion gene polymorphism and interferon-β treatment response in multiple
Smiljana Ristić1, Nada Starčević Čizmarević, Polona Lavtar
1aDepartment of Biology and Medical Genetics bSchool of Medicine, University of Rijeka cDepartment of Neurology, Clinical Hospital Center Rijeka, Rijeka, Croatia dClinical Institute of Medical Genetics eDepartment of Neurology, University Medical Centre, Ljubljana, Slovenia.
Abstract:
We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-β (IFN-β) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-β treated MS patients [162 responders (Rs) and 113 nonresponders (NRs)] were genotyped by PCR. The ACE I/D genotype distribution and allele frequencies did not differ between female Rs and NRs. However, male NRs tended to have a greater prevalence of the DD genotype (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91-7.60) and a significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95% confidence interval: 1.13-5.20) than male Rs. Multiple forward stepwise regression analysis indicated that the negative response to IFN-β therapy was associated with the ACE-DD genotype in men (β=0.371; multiple R change: 0.132; P=0.009) and a higher pretreatment relapse rate in both men (β=-0.438; multiple R change: 0.135; P=0.015) and women (β=-0.208; multiple R change: 0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted for ∼26.7% of the IFN-β response variability among the men in the sample. Further studies of a larger number of MS patients from different populations are necessary to evaluate these preliminary findings.
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