Dataset Information

Decreased expression of the APOA1-APOC3-APOA4 gene cluster is associated with risk of Alzheimer's disease.

ABSTRACT: Apolipoprotein is genetically associated with the risk of Alzheimer's disease (AD). The APOA1, APOC3, and APOA4 genes are closely linked and located on human chromosome 11. Therefore, this gene cluster may be related to the risk of AD.A total of 147 AD patients and 160 healthy controls were randomly recruited from June 2013 to August 2014. APOA1, APOC3, and APOA4 levels were measured using real-time quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay.APOA1, APOC3 and APOA4 levels were significantly lower in AD patients than controls (P<0.01). APOA1, APOC3, and APOA4 levels were negatively related with the severities of AD determined by Clinical Dementia Rating scores (P<0.01). APOA1, APOC3, and APOA4 levels showed a negative relation with Montgomery-Åsberg Depression Rating Scale scores and a positive relation with RAND 36-item health-survey scores (P<0.01). There was a decreased trend for levels of APOA1, APOC3, and APOA4 in AD patients.Low levels of APOA1, APOC3, and APOA4 are associated with risk of AD. APOA1, APOC3, and APOA4 should be developed as combined drugs for the therapy of AD.

SUBMITTER: Lin Q

PROVIDER: S-EPMC4598222 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Decreased expression of the APOA1-APOC3-APOA4 gene cluster is associated with risk of Alzheimer's disease.

Lin Qiao Q Cao Yunpeng Y Gao Jie J

Drug design, development and therapy 20150929

<h4>Background</h4>Apolipoprotein is genetically associated with the risk of Alzheimer's disease (AD). The APOA1, APOC3, and APOA4 genes are closely linked and located on human chromosome 11. Therefore, this gene cluster may be related to the risk of AD.<h4>Patients and methods</h4>A total of 147 AD patients and 160 healthy controls were randomly recruited from June 2013 to August 2014. APOA1, APOC3, and APOA4 levels were measured using real-time quantitative reverse-transcriptase polymerase cha ...[more]

PMID: 26491253

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Project description:OBJECTIVE:The present study investigated the prevalence and risk factors for Metabolic syndrome. We evaluated the association between single nucleotide polymorphisms (SNPs) in the apolipoprotein APOA1/C3/A4/A5 gene cluster and the MetS risk and analyzed the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS. METHODS:A study on the prevalence and risk factors for MetS was conducted using data from a large cross-sectional survey representative of the population of Jilin Province situated in northeastern China. A total of 16,831 participations were randomly chosen by multistage stratified cluster sampling of residents aged from 18 to 79 years in all nine administrative areas of the province. Environmental factors associated with MetS were examined using univariate and multivariate logistic regression analyses based on the weighted sample data. A sub-sample of 1813 survey subjects who met the criteria for MetS patients and 2037 controls from this case-control study were used to evaluate the association between SNPs and MetS risk. Genomic DNA was extracted from peripheral blood lymphocytes, and SNP genotyping was determined by MALDI-TOF-MS. The associations between SNPs and MetS were examined using a case-control study design. The interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS were assessed using multivariate logistic regression analysis. RESULTS:The overall adjusted prevalence of MetS was 32.86% in Jilin province. The prevalence of MetS in men was 36.64%, which was significantly higher than the prevalence in women (29.66%). MetS was more common in urban areas (33.86%) than in rural areas (31.80%). The prevalence of MetS significantly increased with age (OR = 8.621, 95%CI = 6.594-11.272). Mental labor (OR = 1.098, 95%CI = 1.008-1.195), current smoking (OR = 1.259, 95%CI = 1.108-1.429), excess salt intake (OR = 1.252, 95%CI = 1.149-1.363), and a fruit and dairy intake less than 2 servings a week were positively associated with MetS (P<0.05). A family history of diabetes (OR = 1.630, 95%CI = 1.484-1.791), cardiovascular disease or cerebral diseases (OR = 1.297, 95%CI = 1.211-1.389) was associated with MetS. APOA1 rs670, APOA5 rs662799 and rs651821 revealed significant differences in genotype distributions between the MetS patients and control subjects. The minor alleles of APOA1 rs670, APOA5 rs662799 and rs651821, and APOA5 rs2075291 were associated with MetS (P<0.0016). APOA1 rs5072 and APOC3 rs5128, APOA5 rs651821 and rs662799 were in strong linkage disequilibrium to each other with r2 greater than 0.8. Five haplotypes were associated with an increased risk of MetS (OR = 1.23, 1.58, 1.80, 1.90, and 1.98). When we investigated the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster gene polymorphisms, we found that APOA5 rs662799 had interactions with tobacco use and alcohol consumption (PGE<0.05). CONCLUSIONS:There was a high prevalence of MetS in the northeast of China. Male gender, increasing age, mental labor, family history of diabetes, cardiovascular disease or cerebral diseases, current smoking, excess salt intake, fruit and dairy intake less than 2 servings a week, and drinking were associated with MetS. The APOA1/C3/A4/A5 gene cluster was associated with MetS in the Han Chinese. APOA5 rs662799 had interactions with the environmental factors associated with MetS.

Project description:BACKGROUND: Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known. METHOD: The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) ?25?kg?m(-2)) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined. PATIENTS: Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments. RESULTS: APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender-genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014-0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR ?1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87-22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007). CONCLUSION: This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

Project description:Objective: Abnormal lipid metabolism has a close link to the pathophysiology of schizophrenia (SZ). This study mainly aimed to evaluate the association of variants at apolipoprotein A1 (APOA1) and APOA4 with SZ in a Chinese Han population. Methods: The rs5072 of APOA1 and rs1268354 of APOA4 were examined in a case-control study involving 2,680 patients with SZ from the hospital and 2,223 healthy controls screened by physical examination from the community population. The association was estimated with the odds ratio (OR) and 95% confidence intervals (95% CIs) by logistic regression. The APOA1 and APOA4 messenger RNA (mRNA) in peripheral blood leukocytes were measured by real-time PCR and compared between SZ cases and controls. Serum apoA1 levels were detected by turbidimetric inhibition immunoassay and high-density lipoprotein cholesterol (HDL-C) levels were detected by the homogeneous method. Results: Both of the rs5072 of APOA1 and rs1268354 of APOA4 had statistically significant associations with SZ. After adjustment for age and sex, ORs (95% CIs) of the additive model of rs5072 and rs1268354 were 0.82 (0.75-0.90) and 1.120 (1.03-1.23), and p-values were 3.22 × 10-5 and 0.011, respectively. The association of rs5072 with SZ still presented statistical significance even after Bonferroni correction (p-value×6). SZ patients during the episode presented lower levels of apoA1, HDL-C, mRNA of APOA1 common variants and transcript variant 4, and APOA4 mRNA than controls (p < 0.01) while SZ patients in remission showed a significantly decreased APOA1 transcript variant 3 expression level and increased APOA4 mRNA expression level (p < 0.01). mRNA expression levels of APOA1 transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (p trend = 0.017). After the SZ patients received an average of 27.50 ± 9.90 days of antipsychotic treatment, the median (interquartile) of serum apoA1 in the SZ episode significantly increased from 1.03 (1.00.1.20) g/L to 1.08 (1.00.1.22) g/L with the p-value of 0.044. Conclusion: Our findings suggest that the genetic variations of APOA1 rs5072 and APOA4 rs1268354 contribute to the susceptibility of SZ, and the expression levels of APOA1 and APOA4 mRNA of peripheral blood leukocytes decreased in SZ patients during the episode while APOA4 increased after antipsychotic treatment.

Project description:BackgroundDyslipidemia contributes to the risk of many diseases, including stroke, cardiovascular disease and metabolic-related diseases. Previous studies have indicated that single nucleotide polymorphisms (SNPs) are associated with different levels of serum lipid. Therefore, this study explored the relationship between the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms and dyslipidemia in the total sample population and stratified by genders in a northeast Chinese population.MethodsA total of 3,850 participants from Jilin Province, China, were enrolled in our study, and their serum lipid levels were measured. Six functional SNPs (APOA1 rs5072, APOC3 rs5128, APOA4 rs5104, APOA5 rs651821, ZPR1 rs2075294 and BUD13 rs10488698) were genotyped using polymerase chain reaction and MALDI-TOF-MS. Logistic regression analysis was performed to explore the relationship of APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms with dyslipidemia. Linkage disequilibrium and haplotype analyses were performed with the SNPStats program and Haploview software.ResultsAll SNPs conformed to Hardy-Weinberg equilibrium. Logistic regression analysis revealed that rs5072, rs5128 and rs651821 were associated with hypertriglyceridemia, rs5104 and rs651821 were associated with low-HDL cholesterolemia in overall group. rs651821 was associated with hypertriglyceridemia and low-HDL cholesterolemia in both the male and female group. However, among females, rs5072 was observed to be associated with hypertriglyceridemia. Haplotype analysis showed that haplotypes TGCCGC and CAGCGC were associated with dyslipidemia in the overall, male and female groups.ConclusionSNPs in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster were associated with dyslipidemia. Furthermore, the association of APOA1 rs5072 in this gene cluster with dyslipidemia differed between genders; thus, additional studies are needed to confirm this conclusion, and the mechanisms underlying these results warrant further exploration.

Dataset Information

Decreased expression of the APOA1-APOC3-APOA4 gene cluster is associated with risk of Alzheimer's disease.

Publications

Decreased expression of the APOA1-APOC3-APOA4 gene cluster is associated with risk of Alzheimer's disease.

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