Dataset Information

ALDH2 rs671 polymorphisms and the risk of cerebral microbleeds in Chinese elderly: the Taizhou Imaging Study.

ABSTRACT: Background:Cerebral microbleeds (CMBs) are more prevalent in Asian populations, and have been associated with increased risk of stroke, dementia and mortality. So far, risk factors for CMBs other than hypertension were merely known. Previous studies have shown that polymorphisms at aldehyde dehydrogenase 2 (ALDH2) gene were independently associated with the risk of stroke. Its role in CMBs, however, remains unclear. This study aimed to evaluate the associations of ALDH2 gene polymorphisms with CMBs in Chinese elderly. Methods:Using bio-specimen and data collected at baseline survey of the population-based Taizhou Imaging Study (TIS) (phase I), we genotyped the single nucleotide polymorphisms (SNPs) at ALDH2 among 549 individuals aged 55-65 years, and rs671 was used as surrogate marker of ALDH2. CMBs were detected on brain magnetic resonance imaging (MRI), and further categorized as strictly lobar or as deep/mixed. Logistic regression models were used to evaluate the associations of the variants at ALDH2 and CMBs. Results:CMBs were present in 103 individuals (18.8%). Forty-one point three percent participants were with ALDH2 *2 allele and 5.1% had ALDH2 *2/*2 genotype. Subjects with ALDH2 *1 allele were more likely to be drinker, have hypertension or CMBs than those with *2 allele (all P<0.05). Multivariate logistic regression model showed that the ALDH2 *1/*1 genotype was independently associated with CMBs (P=0.013), particularly for deep/mixed CMBs (P=0.008), and the association was more pronounced in men, non-drinkers or hypertension patients. Conclusions:The results suggest that Han Chinese with ALDH2 *1/*1 genotype may be more susceptible to CMBs than those with ALDH2 *2 allele.

SUBMITTER: Zhu Z

PROVIDER: S-EPMC7154495 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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<i>ALDH2</i> rs671 polymorphisms and the risk of cerebral microbleeds in Chinese elderly: the Taizhou Imaging Study.

Zhu Zhen Z Jiang Yanfeng Y Cui Mei M Wang Yingzhe Y Li Shuyuan S Xu Kelin K Zhang Kexun K Zhu Chengkai C Xu Wanghong W Jin Li L Ye Weimin W Suo Chen C Chen Xingdong X

Annals of translational medicine 20200301 5

<h4>Background</h4>Cerebral microbleeds (CMBs) are more prevalent in Asian populations, and have been associated with increased risk of stroke, dementia and mortality. So far, risk factors for CMBs other than hypertension were merely known. Previous studies have shown that polymorphisms at aldehyde dehydrogenase 2 (<i>ALDH</i>2) gene were independently associated with the risk of stroke. Its role in CMBs, however, remains unclear. This study aimed to evaluate the associations of <i>ALDH</i>2 gen ...[more]

PMID: 32309376

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Project description:IMPORTANCE:Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. OBJECTIVE:To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, ?-amyloid (A?), and cognition. DESIGN, SETTING, AND PARTICIPANTS:A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. INTERVENTIONS:3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar A?. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. MAIN OUTCOMES AND MEASURES:Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and A? were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. RESULTS:The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P?=?.0003), with the largest reductions in the parietal cortex (-37.6%; P?<?.0001) and precuneus (-31.8%; P?=?.0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P?=?.047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P?=?.12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P?=?.60). CONCLUSIONS AND RELEVANCE:In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.

Project description:BackgroundHypertensive patients have a younger trend, and studies on the role of genetic factors in hypertension susceptibility have been inconsistent. Aldehyde dehydrogenases 2 (ALDH2) and apolipoprotein E (APOE) are involved in the pathophysiological processes of hypertension. To investigate the relationship of ALDH2 and APOE polymorphisms with hypertension in middle-aged (30-59 years old) and elderly (≥60 years old) persons.MethodsTwo thousand six hundred and ten hypertensive patients and 1921 controls were included (between 30 and 100 years old). The genotypes of common polymorphisms in APOE and ALDH2 genes (APOE rs429358, rs7412, and ALDH2 rs671) of the subjects were analyzed by polymerase-chain reaction (PCR)-microarray. Statistical analyses (Student's t-test, Mann-Whitney U-test, χ 2 test, and logistic regression analysis) were performed with SPSS v21.0.ResultsThere were 4531 participants (66.60 ± 12.10 years old) in this study, including 3057 (67.5%) males and 1474 (32.5%) females. There were no significant differences in distributions of ALDH2 rs671, APOE rs429358/rs7412 genotypes and alleles between hypertensive patients and controls. Persons with ALDH2 rs671 G/A or A/A genotype were less likely to have hypertension (G/A+A/A vs G/G: gender-, age-, smoking-, and drinking-adjusted OR 0.885, 95% CI 0.785-0.997, P=0.045), while ALDH2 rs671 A/A+APOE rs429358 or rs7412 wild-type genotype may decrease the risk of hypertension. In middle-aged group, ALDH2 rs671 G/A+APOE rs429358 T/C carriers (adjusted OR 0.547, 95% CI 0.350-0.856, P=0.008), and ALDH2 rs671 A/A+APOE rs7412 C/C genotypes (adjusted OR 0.567, 95% CI 0.361-0.891, P=0.014) were less likely to have hypertension. In elderly group, APOE rs7412 T/T carriers were more likely to have hypertension (rs671 T/T vs C/C: adjusted OR 4.755, 95% CI 1.075-21.027, P=0.040; rs671 T/T vs C/C or C/T: adjusted OR 4.734, 95% CI 1.071-20.928, P=0.040).ConclusionPolymorphism-polymorphism interactions of ALDH2 rs671 and APOE rs429358/rs7412 may effect on hypertension susceptibility. Different genotypes comparison shows different roles in middle-aged and elderly people, respectively.

Dataset Information

ALDH2 rs671 polymorphisms and the risk of cerebral microbleeds in Chinese elderly: the Taizhou Imaging Study.

Publications

<i>ALDH2</i> rs671 polymorphisms and the risk of cerebral microbleeds in Chinese elderly: the Taizhou Imaging Study.

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