Yoon Cindy W, Kim Jonguk, Suh Young Ju, Kim Byeong C, Youn Young Chul, Jeong Jee Hyang, Han Hyun Jeong, Choi Seong Hye
Department of Neurology, Inha University School of Medicine, Incheon, Republic of Korea.
Department of Biomedical Sciences, Inha University School of Medicine, Incheon, Republic of Korea.
Front Neurol. 2023 Oct 12;14:1230141. doi: 10.3389/fneur.2023.1230141. eCollection 2023.
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.
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.
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%; = 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]; 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]; 0.02).
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.
血管紧张素转换酶（ACE）插入/缺失（I/D）多态性已被作为脑小血管病（CSVD）的一个基因候选因素进行研究。然而，此前尚无研究评估ACE I/D多态性与脑微出血（CMB，一种重要的CSVD标志物）之间的关系。我们评估了ACE I/D多态性与CMB两年变化之间的关联。
对CHALLENGE（西洛他唑与阿司匹林对脑小血管病白质病变体积变化的比较研究）数据库进行分析。在256名受试者中，纳入了186名接受了为期两年的脑部随访扫描及ACE基因分型的参与者。我们的分析是在假设D等位基因具有隐性效应的情况下，将ACE基因型分为两组（DD与ID/II）进行的。采用线性混合效应模型比较DD基因型与ID/II合并基因型之间CMB数量的两年变化情况。
在本研究纳入的186例患者中，24例（12.9%）为DD基因型，91例（48.9%）为ID基因型，71例（38.2%）为II基因型。除高血压患病率外（DD为66.7%，ID/II为84.6%；P = 0.04），两组（DD与ID/II）的基线临床特征和脑小血管病标志物无差异。多变量线性混合效应模型显示，在对CMB的基线数量、年龄、性别和高血压进行校正后，DD基因型携带者的总CMB计数增加幅度大于ID/II基因型携带者（差异估计均值[标准误（SE）]=1.33[0.61]；P = 0.03）。当我们对分为深部和叶部CMB的病例进行分析时，两组之间仅叶部CMB存在显著差异（差异估计均值[SE]=0.94[0.42]；P = 0.02）。
与II/ID合并基因型携带者相比，ACE DD基因型携带者的CMB在两年内进展更大。我们的研究结果表明ACE I/D多态性与CMB之间可能存在关联。需要进行更大样本量的研究来证实这种关联。
