Dataset Information

Association of genetic variants of CELSR1 and 3q28 with hypertension in community-dwelling individuals.

ABSTRACT: Findings of previous studies demonstrated that rs6007897 (C?T, Ala2268Thr) of the cadherin, epidermal growth factor (EGF) laminin A G-type repeats (LAG) seven-pass G-type receptor 1 gene (CELSR1) and rs9846911 (A?G) at chromosome 3q28 were significantly associated with ischemic stroke and chronic kidney disease, respectively. Given that hypertension is a risk factor for both ischemic stroke and chronic kidney disease, it was hypothesized that the association of rs6007897 with ischemic stroke or of rs9846911 with chronic kidney disease might be attributable, at least in part, to their effects on genetic susceptibility to hypertension. The purpose of the present study was to examine a possible association of rs6007897 of CELSR1 or rs9846911 at 3q28 with hypertension in community-dwelling individuals. Study subjects comprised 5,959 community-dwelling individuals (1,670 subjects with hypertension and 4,289 controls) who were recruited to a population-based cohort study. Comparisons of allele frequencies by the Chi-square test revealed that rs6007897 of CELSR1 (P=0.0280) and rs9846911 at 3q28 (P=0.0171) were significantly associated with the prevalence of hypertension. Multivariate logistic regression analysis with adjustment for age, gender, body mass index (BMI), smoking status, the serum concentration of creatinine and the prevalence of dyslipidemia and diabetes mellitus revealed that rs6007897 (P=0.0308; recessive model; odds ratio, 1.56) and rs9846911 (P=0.0353; dominant model; odds ratio, 1.22) were significantly associated with hypertension with the T allele rs6007897 and the G allele rs984691 representing risk factors for this condition. CELSR1 and 3q28 may thus be susceptibility loci for hypertension.

SUBMITTER: Ueyama C

PROVIDER: S-EPMC3917012 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Association of genetic variants of <i>CELSR1</i> and 3q28 with hypertension in community-dwelling individuals.

Ueyama Chikara C Horibe Hideki H Fujimaki Tetsuo T Oguri Mitsutoshi M Kato Kimihiko K Yamada Yoshiji Y

Biomedical reports 20130924 6

Findings of previous studies demonstrated that rs6007897 (C→T, Ala2268Thr) of the cadherin, epidermal growth factor (EGF) laminin A G-type repeats (LAG) seven-pass G-type receptor 1 gene (<i>CELSR1</i>) and rs9846911 (A→G) at chromosome 3q28 were significantly associated with ischemic stroke and chronic kidney disease, respectively. Given that hypertension is a risk factor for both ischemic stroke and chronic kidney disease, it was hypothesized that the association of rs6007897 with ischemic str ...[more]

PMID: 24649039

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Project description:STUDY OBJECTIVES:The objective of this study was to determine which respiratory and architectural sleep parameters are related to cognitive function and cognitive status (mild cognitive impairment [MCI] versus normal cognitive aging [NCA]) in community-dwelling individuals with hypertension. Additionally, it aimed to determine whether the results changed in the presence or absence of vascular brain lesions (silent brain infarcts and extensive white matter hyperintensities [WMHs]). METHODS:In a cohort of individuals with hypertension and without previous stroke or dementia, we conducted in-hospital polysomnography including electroencephalography, electro-oculography, electromyography, and magnetic resonance imaging to assess silent brain infarcts and WMHs. Cognitive testing was carried out with a screening test (Dementia Rating Scale version 2 [DRS-2]) and a complete cognitive visit. RESULTS:This study included 158 participants with a median age of 65.0 years; 32.3% were females, and the median apnea-hypopnea index was 22.3 events/h. MCI was diagnosed in 24 study participants, and the rest had NCA. Regarding respiratory parameters, total DRS-2 scores (?; 95% CI) 0.121; 0.026, 0.215 were positively associated with mean O? saturation, whereas total (-0.022; -0.036, -0.009), executive function (-0.016; -0.026, -0.006) and memory (-0.017; -0.029, -0.004) DRS-2 scores were all negatively associated with the percent of time with oxygen saturation < 90% after correcting for education, vascular risk factors, and magnetic resonance imaging lesions. Regarding sleep architecture, Attention DRS-2 scores (0.0153; 0.001, 0.306) were independently associated with total sleep time. Similar results were obtained in the absence of silent brain infarcts or WMHs in the stratified analysis. None of the sleep parameters were associated with cognitive status. CONCLUSIONS:Low oxygen saturation contributes to cognitive performance, and this effect appears even in the absence of vascular brain lesions in individuals with hypertension.

Project description:The associations among cognitive function, hypertension, and dyslipidemia in older adults are controversial. Therefore, we investigated the associations among cognitive decline, hypertension, dyslipidemia, and their combination in community-dwelling older people in their 70s, 80s, and 90s in the long-term observational Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. We administered the Montreal Cognitive Assessment Japanese version (MoCA-J) by trained geriatricians and psychologists, and conducted blood testing and blood pressure (BP) measuring by medical staff involving 1186 participants. We performed multiple regression analysis to assess the relationships among hypertension, dyslipidemia, their combination, and lipid and BP levels with cognitive function at the 3-year follow-up after adjusting for covariate factors. At the baseline, the percentage of the combination of hypertension and dyslipidemia was 46.6% (n = 553), hypertension was 25.6% (n = 304), dyslipidemia was 15.0% (n = 178), and that without hypertension or dyslipidemia was 12.7% (n = 151). Conducting multiple regression analysis, no significant correlation was found between the combination of hypertension and dyslipidemia and MoCA-J score. In the group with the combination, high high-density lipoprotein cholesterol (HDL) levels resulted in higher MoCA-J scores at the follow-up (β = 0.06; P < 0.05) and high diastolic BP (DBP) also resulted in higher MoCA-J scores (β = 0.08; P < 0.05). The results suggest that high HDL and DBP levels of individuals with HT & DL and high SBP levels of individuals with HT were associated with cognitive function in community-dwelling older adults. In the SONIC study, which is an epidemiological study of Japanese older persons aged 70 years or older, a disease-specific examination suggested that high HDL and DBP levels of individuals with hypertension & dyslipidemia and high SBP levels of individuals with hypertension were associated with maintaining cognitive function in community-dwelling older adults.

Dataset Information

Association of genetic variants of CELSR1 and 3q28 with hypertension in community-dwelling individuals.

Publications

Association of genetic variants of <i>CELSR1</i> and 3q28 with hypertension in community-dwelling individuals.

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