Dataset Information

Associations of Oxidative Phosphorylation-Related Genes With Deep Intracerebral Hemorrhage in Taiwan.

ABSTRACT: Background:Pathway analysis demonstrated associations between deep intracerebral hemorrhage (DICH) and the genetic risk score of complex IV of the oxidative phosphorylation (OXPHOS) pathway in whites. This study investigated the related genetic variations in the DICH population in Taiwan. Candidate variants were selected from the prior report by the following criteria: (1) nuclear genes encoding mitochondria complex IV, (2) genetic effect >1.08, (3) global minor allele frequency >0.01. Six single-nucleotide polymorphisms fitted in the selection criteria, which were mainly involved in Cox assembly, including Cox10, Cox15, and Cox18, and one structural gene, Cox7C. Associations were tested with adjustment of multiple covariables. Permutation testing of 1000 replicates was performed for empirical estimates. Results:This study enrolled 336 patients and 379 controls. Compared with whites, the Taiwan population has higher minor allele frequency (MAF) of rs4308511, rs767844, and rs221592 and lower MAF of rs8079640. There was no variation of rs16949067 in the Taiwan population. When adjusting for the traditional risk factors, rs221592 G allele was associated with DICH risk in women under additive (odds ratio (OR)?=?1.5, 95% confidence interval (CI)?=?1.02-2.3, P?=?.04) and recessive models (OR?=?2.9, 95% CI?=?1.2-6.9, P?=?.013). In an additive fashion, a poor 30-day outcome was associated with rs4308511 T allele (OR?=?1.6, 95% CI?=?1.1-2.3, P?=?.014) and rs9891372 C allele (OR?=?1.7, 95% CI?=?1.05-2.8, P?=?.024) in all subjects and in men (rs4308511, OR?=?1.8, 95% CI?=?1.2-2.7, P?=?.008; rs9891372, OR?=?2.1, 95% CI?=?1.1-3.8, P?=?.02). Conclusions:The results showed ethnic disparities in the complex IV-related genes. COX18-rs221592 G allele was associated with female DICH risks. COX7C-rs4308511 T allele was an independent risk of poor outcome in men.

SUBMITTER: Chen YC

PROVIDER: S-EPMC6104204 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Associations of Oxidative Phosphorylation-Related Genes With Deep Intracerebral Hemorrhage in Taiwan.

Chen Yi-Chun YC Chen Chiung-Mei CM Lee Yun-Shien YS Chang Kuo-Hsuan KH

Journal of experimental neuroscience 20180821

<h4>Background</h4>Pathway analysis demonstrated associations between deep intracerebral hemorrhage (DICH) and the genetic risk score of complex IV of the oxidative phosphorylation (OXPHOS) pathway in whites. This study investigated the related genetic variations in the DICH population in Taiwan. Candidate variants were selected from the prior report by the following criteria: (1) nuclear genes encoding mitochondria complex IV, (2) genetic effect >1.08, (3) global minor allele frequency >0.01. S ...[more]

PMID: 30150875

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Project description:Spontaneous intracerebral hemorrhage (ICH) is a devastating stroke subtype. Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and the activities of MMPs are modulated by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). This study aimed to discuss relationship of MMP-2 and TIMP-2 to spontaneous deep ICH (SDICH) susceptibility and hematoma size.Associations were tested by logistic regression and general linear models (GLM) where appropriate, adjusting with covariables of age, sex, hypertension, diabetes mellitus, smoking, and alcohol consumption. Association analyses were performed first by stratification of genders and then by the age of 65 years old (y/o). Elder population was defined as subjects who were older than 65 y/o.There were 396 SDICH patients and 376 control subjects in this study. In the elder group, rs7503607 C>A variant in TIMP-2 was associated with SDICH in male and overall patients (OR = 3.49, 95% CI 1.45 to 8.40, P = 0.005 and OR = 2.45, 95% CI 1.37 to 4.38, P = 0.003, respectively) in additive genetic model. In recessive genetic model, rs2285053 TT genotype in MMP-2 was correlated to SDICH in male patients and overall elder group (OR = 7.30, 95% CI 1.3 to 40, P = 0.02 and OR = 2.91, 95% CI 1.02 to 8.31, P = 0.046, respectively), and rs7503726 AA genotype in TIMP-2 was associated with SDICH in female patients (OR = 0.29, 95% CI 0.1 to 0.84, P = 0.02). In younger male and overall younger patients, SDICH patients who had supratentorial hemorrhage had significantly lower frequency of AA genotypes in rs7503726 than those with infratentorial hemorrhage (OR = 0.36, 95% CI 0.17 to 0.75, P = 0.006 and OR = 0.43, 95% CI 0.22 to 0.84, P = 0.014, respectively). Hemorrhage size increased by 9.7 (95% CI 2.1 to 43, P = 0.004) cm3 per minor allele (A) of the rs7503607 variant in the elder female patients and increased by 4.3 (95% CI 1.4 to 12.9, P = 0.009) cm3 per minor allele (A) in all elder patients. In younger patients, the hemorrhage size decreased by 3.3 (95% CI 1.2 to 9.5, P = 0.03) cm3 per minor allele of the s7503726 variant in the female patients.This study showed a significant association between the variants of MMP-2 and TIMP-2 promoters and SDICH susceptibility with significant age and gender differences. Hemorrhage location and size might be affected by TIMP-2 promoter variants in the SDICH patients.

Project description:BackgroundSpontaneous deep intracerebral hemorrhage (SDICH) is a devastating stroke subtype. The causes of SDICH are heterogeneous. Matrix metalloproteinase-9 (MMP-9, Gelantinase B) has been shown to relate to stroke and the development of aneurysm and may increase risks of intracerebral hemorrhage. MMP activities are modulated by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). We analyzed the genetic variants of MMP-9 and TIMP-1 and SDICH susceptibility.MethodsAssociations were tested by logistic regression or general linear models with adjusting for multiple covariables. Multiplicative terms between genes were applied to detect the interaction effects on SDICH. Permutation testing of 1,000 replicates was performed for empirical estimates.ResultsIn the group of ≥65 years old (y/o), we found associations of SDICH with rs3787268 (Odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.27 to 0.86, P = 0.01) and haplotype1 (Hap1) (OR = 0.48, 95% CI 0.26 to 0.86, P = 0.014). For TIMP1 gene, rs4898 was associated with SDICH in the elder male group (OR = 0.35, 95% CI 0.15 to 0.81, P = 0.015). In contrast, in the younger male group, there were associations of SDICH with rs2250889 (OR = 0.48, 95% CI 0.27 to 0.84, P = 0.01) and Hap3 (OR = 0.61, 95% CI 0.38 to 0.97, P = 0.04). We found significant genetic interaction between TIMP-1 and MMP-9 in SDICH susceptibility among younger male subjects (P = 0.004). In subjects carrying rs4898 minor allele, carriers with Hap3 had lower SDICH risk than non-carriers (OR = 0.19, 95% CI 0.07 to 0.51, P = 0.001). In addition, this study showed that when young males were exposed to alcohol, Hap3 was a protective factor of SDICH (OR = 0.06, 95% CI 0.01 to 0.27, P = 0.0002). In contrast, when they were exposed to smoke, Hap2 carriers had increased risk of SDICH (OR = 2.45, 95% CI 1.05 to 5.73, P = 0.04).ConclusionsThis study showed modest to moderate effects of MMP-9 and TIMP-1 polymorphisms on SDICH risks with significant age differences. MMP-9 may interact with alcohol to play a role in the SDICH risk in young men.

Project description:ObjectiveHematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH.MethodsPooled analysis of individual patient data between January 2006 and December 2015 from a German-wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single-center registry (UKER-ICH) investigating non-OAC-ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin-K-antagonists (VKA, n = 1186) and non-vitamin-K-antagonist-oral-anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3-month functional outcome.ResultsOccurrence of HE was not different after deep versus lobar ICH in patients with non-OAC-ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA-ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC-ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non-OAC-ICH (deep:+59% [40-122] vs. lobar:+74% [37-124], P = 0.65), but both patients with VKA-ICH and NOAC-ICH showed greater HE extent after deep ICH [VKA-ICH, deep: +94% [54-199] vs. lobar: +56% [35-116], P < 0.001; NOAC-ICH, deep: +74% [56-123] vs. lobar: +40% [21-49], P = 0.001). Deep compared to lobar ICH patients had higher HE hazard during first 13.5 h after onset (Hazard ratio [HR]: 1.85 [1.03-3.31], P = 0.04), followed by lower hazard (13.5-26.5 h, HR: 0.46 [0.23-0.89], P = 0.02), and equal hazard thereafter (HR: 0.96 [0.56-1.65], P = 0.89). Odds ratio for unfavorable outcome was higher after HE in deep (4.31 [2.71-6.86], P < 0.001) versus lobar ICH (2.82 [1.71-4.66], P < 0.001), and only significant after small-medium (1st volume-quarter, deep: 3.09 [1.52-6.29], P < 0.01; lobar: 3.86 [1.35-11.04], P = 0.01) as opposed to large-sized ICH (4th volume-quarter, deep: 1.09 [0.13-9.20], P = 0.94; lobar: 2.24 [0.72-7.04], P = 0.17).InterpretationHE occurrence does not differ among deep and lobar ICH. However, compared to lobar ICH, HE after deep ICH is of greater extent in OAC-ICH, occurs earlier and may be of greater clinical relevance. Overall, clinical significance is more apparent after small-medium compared to large-sized bleedings.

Project description:BackgroundIntraventricular hemorrhage (IVH) after intracerebral hemorrhage (ICH) is a strong independent predictor of poor outcomes. Although the location and volume of ICH are associated with IVH, our knowledge concerning the mechanism of IVH after ICH is still limited. This study aimed to investigate the relationship between hematoma morphology and IVH in patients with supratentorial deep ICH.MethodsWe retrospectively analyzed adult patients (aged ≥18 years) with spontaneous supratentorial deep ICH who underwent computed tomography (CT) within 48 h after ICH symptom onset in Peking University First Hospital between January 2017 and August 2022. We collected the clinical and imaging data of the patients and assessed hematoma morphology using several quantitative radiological parameters including hematoma volume, sphericity index, A/B ratio (A: the largest area of hematoma; B: the largest diameter 90° to A on the same slice), and our newly proposed largest diameter-midline angle (LMA). Multivariable logistic regression analysis was used to analyze the relationship between these parameters and the presence of IVH on the initial CT scan.ResultsAmong 114 patients with spontaneous supratentorial deep ICH, 41 (36.0%) had IVH. In patients with IVH, the sphericity index was lower than that in individuals without IVH, while the LMA was larger. Multivariate logistic regression analysis showed that sphericity index [0.1-unit odds ratio (OR) =0.252; 95% CI: 0.089-0.709; P=0.009] and the LMA (10-unit OR =1.281; 95% CI: 1.007-1.630; P=0.04) were independently associated with the presence of IVH in patients with supratentorial deep ICH. Univariate analyses showed that hematoma volume, A/B ratio, sphericity index, and the LMA were significantly associated with poor outcomes at discharge.ConclusionsTwo quantitative parameters of hematoma morphology, sphericity index and the LMA, were significantly associated with the presence of IVH in patients with supratentorial deep ICH. Further prospective studies with larger sample sizes are needed to validate our results.

Dataset Information

Associations of Oxidative Phosphorylation-Related Genes With Deep Intracerebral Hemorrhage in Taiwan.

Publications

Associations of Oxidative Phosphorylation-Related Genes With Deep Intracerebral Hemorrhage in Taiwan.

Similar Datasets

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