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Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds

BACKGROUND AND PURPOSE: The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed...

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Autores principales: Yoon, Cindy W., Kim, Jonguk, Suh, Young Ju, Kim, Byeong C., Youn, Young Chul, Jeong, Jee Hyang, Han, Hyun Jeong, Choi, Seong Hye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602736/
https://www.ncbi.nlm.nih.gov/pubmed/37900609
http://dx.doi.org/10.3389/fneur.2023.1230141
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author Yoon, Cindy W.
Kim, Jonguk
Suh, Young Ju
Kim, Byeong C.
Youn, Young Chul
Jeong, Jee Hyang
Han, Hyun Jeong
Choi, Seong Hye
author_facet Yoon, Cindy W.
Kim, Jonguk
Suh, Young Ju
Kim, Byeong C.
Youn, Young Chul
Jeong, Jee Hyang
Han, Hyun Jeong
Choi, Seong Hye
author_sort Yoon, Cindy W.
collection PubMed
description BACKGROUND AND PURPOSE: The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs. METHODS: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes. RESULTS: Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02). CONCLUSION: The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.
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spelling pubmed-106027362023-10-27 Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds Yoon, Cindy W. Kim, Jonguk Suh, Young Ju Kim, Byeong C. Youn, Young Chul Jeong, Jee Hyang Han, Hyun Jeong Choi, Seong Hye Front Neurol Neurology BACKGROUND AND PURPOSE: The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs. METHODS: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes. RESULTS: Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02). CONCLUSION: The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association. Frontiers Media S.A. 2023-10-12 /pmc/articles/PMC10602736/ /pubmed/37900609 http://dx.doi.org/10.3389/fneur.2023.1230141 Text en Copyright © 2023 Yoon, Kim, Suh, Kim, Youn, Jeong, Han and Choi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Yoon, Cindy W.
Kim, Jonguk
Suh, Young Ju
Kim, Byeong C.
Youn, Young Chul
Jeong, Jee Hyang
Han, Hyun Jeong
Choi, Seong Hye
Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
title Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
title_full Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
title_fullStr Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
title_full_unstemmed Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
title_short Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
title_sort angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602736/
https://www.ncbi.nlm.nih.gov/pubmed/37900609
http://dx.doi.org/10.3389/fneur.2023.1230141
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