Angiotensin-converting enzyme insertion/deletion gene polymorphism and interferon-β treatment response in multiple sclerosis patients

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.

Could angiotensin-converting enzyme 1 I/D polymorphism be a modificator of COVID-19 response in different populations, diseases, and/or conditions?

“…In the past 15 years, our study groups have been investigating the possible relevance of the ACE1 I/D polymorphism in various diseases and/or conditions in the Croatian population. Most of our studies suggest that the ACE1 D allele as well as the ACE1 D/D genotype may be risk factors in multiple sclerosis, 7 , 8 schizophrenia, 9 and lung cancer. 10 Importantly, we have also found that the risk effects of the ACE1 D allele and ACE1 D/D genotype were in general more prominent among male patients with multiple sclerosis 7 , 8 and schizophrenia.…”

“…Most of our studies suggest that the ACE1 D allele as well as the ACE1 D/D genotype may be risk factors in multiple sclerosis, 7 , 8 schizophrenia, 9 and lung cancer. 10 Importantly, we have also found that the risk effects of the ACE1 D allele and ACE1 D/D genotype were in general more prominent among male patients with multiple sclerosis 7 , 8 and schizophrenia. 9 Indeed, COVID-19 infection has previously been associated with sex, 11 and a recent article discussing the angiotensin-converting enzyme 2 (encoded by the ACE2 gene), which has been known to cooperate with ACE1 in the renin–angiotensin system, hypothesizes that sex differences in COVID-19 severity may be related to the ACE1 and ACE2 genes.…”

Genetic Variations of Angiotensinogen, Angiotensin Converting Enzyme, and Angiotensin Type 1 Receptor with the Risk of Pulmonary Tuberculosis

“…ACE polymorphism may influence the serum level of ACE. A functional insertion/deletion (I/D) polymorphism in the ACE gene has been recognized (Ristic et al, 2017). The ACE insertion/deletion (I/D) polymorphism is based on a 287bp Alu repeat sequence within intron 16 (Gong et al, 2012;Yigit et al, 2013).…”