Apolipoprotein A-V

载脂蛋白 A - V
  • 文章类型: Journal Article
    2型糖尿病(T2DM)是一种多因素疾病,具有很高的全球发病率。高甘油三酯血症是心血管疾病和T2DM的主要危险因素。在这项研究中,我们测定了载脂蛋白A5(APOA5)单核苷酸多态性(SNP)rs662799和perilipin1(PLIN1)SNPsrs894160,rs6496589和rs1052700的等位基因和基因型频率,并评估了它们与西部沙特阿拉伯T2DM风险的相关性.只有rs6496589被发现与T2DM风险显著相关。我们根据相对风险确定了每个SNP的风险等位基因,发现rs662799的G等位基因,rs894160的T等位基因,r6496589的G等位基因和rs1052700的T等位基因与T2DM风险相关。每个SNP对T2DM风险及其5种临床表型的影响使用多元logistic回归分析。我们发现rs6496589的C/G和G/G基因型与T2DM风险之间存在显著相关性。而G/G是校正模型中唯一与T2DM风险相关的基因型.rs662799、rs894160和rs1052700基因型与T2DM风险无显著相干性。总之,我们在沙特西部人群中发现了导致2型糖尿病遗传风险的新风险等位基因和基因型.
    Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a high global incidence. Hypertriglyceridemia is a major risk factor for both cardiovascular disease and T2DM. In this study, we determined the allele and genotype frequencies of apolipoprotein A5 (APOA5) single nucleotide polymorphism (SNP) rs662799 and perilipin 1 (PLIN1) SNPs rs894160, rs6496589, and rs1052700 and evaluated their association with T2DM risk in western Saudis. Only rs6496589 was found to be significantly associated with T2DM risk. We determined the risk allele for each SNP based on relative risk, and found that the G allele of rs662799, T allele of rs894160, G allele of r6496589, and T allele of rs1052700 correlated with T2DM risk. The effect of each SNP on T2DM risk and five of its clinical phenotypes was explored using multiple logistic regression. We found significant correlations between the C/G and G/G genotypes of rs6496589 and T2DM risk in the unadjusted model, whereas G/G was the only genotype that correlated with the risk of T2DM in the adjusted model. There was no significant correlation between rs662799, rs894160, and rs1052700 genotypes and T2DM risk. In conclusion, we have identified novel risk alleles and genotypes that contribute to genetic risk for T2DM in the western Saudi population.
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  • 文章类型: Journal Article
    载脂蛋白A5(APOA5)rs662799与全基因组显著性水平的血脂水平显著相关。肥胖的动态变化是否会影响脂质基因座对长期血脂谱的影响尚不清楚。我们在前瞻性队列中评估了5年体重指数(BMI)变化和rs662799基因型与偶发血脂异常和血脂纵向变化风险的相互作用。
    我们纳入了4329名基线年龄≥40岁的非血脂异常参与者,他们来自一个明确的社区队列,平均随访5年。在基线和随访时测量BMI和血脂。
    每个rs662799A-等位基因与发生血脂异常的风险的相关性随着BMI变化水平的增加而增强,比值比(OR)从BMI变化的最低三分位数(<0.02kg/m2)的1.03增加到第二(0.02-1.29)的1.17,最高三分位数为1.46(>1.29)(pfor交互作用<0.001)。在AA携带者中,BMI(kg/m2)每增加1个单位与血脂异常的关联更为突出(OR=1.50,95CI[1.26-1.80],p<0.001),而在GA(OR=1.10)或GG载体(OR=1.09)中弱得多(pfor相互作用=0.002)。对于高甘油三酯(TG)和低高密度脂蛋白胆固醇(HDL-c)的事件风险也发现了类似的结果。或log10-TG的纵向变化(所有pfor相互作用≤0.02)。
    BMI变化显著调节rs662799对血脂异常和长期血脂的遗传贡献,为根据个体遗传背景对血脂进行个性化临床管理提供了新的证据。
    The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on long-term blood lipid profile remains unclear. We assessed interactions of 5-year body mass index (BMI) change and rs662799 genotypes with risk of incident dyslipidemia and longitudinal changes in serum lipids in a prospective cohort.
    We included 4329 non-dyslipidemia participants aged ≥ 40 years at baseline from a well-defined community-based cohort and followed up for an average of 5 years. BMI and blood lipids were measured at baseline and follow-up.
    The association of each rs662799 A-allele with risk of incident dyslipidemia was stronger along with the increase in BMI change level, with the odds ratios (OR) increasing from 1.03 in the lowest tertile of BMI change (< 0.02 kg/m2) to 1.17 in the second (0.02-1.29), and 1.46 in the highest tertile (> 1.29) (pfor interaction< 0.001). Associations of each 1-unit of BMI (kg/m2) increase with incident dyslipidemia were more prominent in the AA carriers (OR = 1.50, 95%CI [1.26-1.80], p < 0.001), while much weaker in the GA (OR = 1.10) or GG carriers (OR = 1.09) (pfor interaction = 0.002). Similar results were found for the risk of incident higher triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL-c), or the longitudinal changes in log10-TG (all pfor interaction ≤ 0.02).
    BMI changes significantly modulate rs662799 genetic contribution to dyslipidemia and long-term lipid profile, which provide new evidence for personalized clinical management of lipids according to individual genetic background.
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  • 文章类型: Journal Article
    Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs\' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p < 0.0001). Also, single SNP regression results showed that the odds ratios (ORs) for both models are almost similar; however, the p-values had slightly higher significance levels in the HTg-MetS model. The strongest ORs in the HTg-MetS model belonged to the G allele in rs2266788 (MetS: OR = 1.3, p = 3.6 × 10-7; HTg-MetS: OR = 1.4, p = 2.3 × 10-11) and the T allele in rs651821 (MetS: OR = 1.3, p = 2.8 × 10-7; HTg-MetS: OR = 1.4, p = 3.6 × 10-11). In the present study, the kernel machine regression models could help assess the association between the BUD13, ZPR1, and APOA5 gene variants (11p23.3 region) with lipid-related traits in MetS and MetS affected with high TG.
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  • 文章类型: Journal Article
    Plasma triglyceride (TG) concentrations are markedly higher among Asians, which may be associated with the interaction of genetics and lifestyle factors.
    The purpose of this study was to investigate the genetic variants that have a strong association with plasma TG concentrations from genome-wide association study and to identify lifestyle interactions with the genetic variants that are associated with dyslipidemia in a cohort of Korean adults.
    Korean genome and epidemiology study utilized a cross-sectional design of Koreans to determine genetic variants and lifestyle factors, including nutrient intakes, in a retrospective hospital-based city cohort conducted by the Korean Center for Disease and Control during 2004-2013.
    Korean adults aged 40 to 77 years were participants (n=28,445).
    The genetic variants that influence plasma TG concentrations were selected by genome-wide association study using an allele genetic model after adjusting for age, sex, area of residence, and body mass index. Lipid profiles and nutrient intakes from food frequency questionnaires were measured. The interactions between the single nucleotide polymorphisms and lifestyle factors were determined to influence plasma TG levels.
    Carrying the minor alleles of APOA5 rs662799 and rs2266788 had an association with higher plasma TG concentrations by 1.86- and 1.51-fold, respectively, compared with those with the major allele (P=8.89E-150 and P=4.75E-68, respectively). Sex had an interaction with these single nucleotide polymorphisms, with males having higher plasma TG concentrations. The single nucleotide polymorphisms had significant interactions with carbohydrate, fat, and calcium intakes; alcohol consumption; and smoking status that were associated with plasma TG concentrations. Carriers with the minor allele of each single nucleotide polymorphisms had higher plasma TG concentrations when consuming-low fat (<15%) and high carbohydrate (≥72%) diets than those with major alleles. Carriers of the minor alleles with low calcium intakes (<500 mg/day) experienced elevated plasma TG concentrations compared with carriers of the major alleles. Smokers and alcohol drinkers with either of the minor alleles of APOA5, rs662799 or rs2266788, had higher plasma TG concentrations than those with its major allele.
    These results indicated that carrying the minor alleles of APOA5 rs662799 and rs2266788, especially for men, was associated with elevated TG concentrations and suggested that Korean carriers of the minor alleles could be at increased risk of hypertriglyceridemia. Further research is needed to investigate the efficacy of modulating lifestyle factors to prevent dyslipidemia in people carrying the minor alleles of APOA5 rs662799 and rs2266788.
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  • 文章类型: Journal Article
    UNASSIGNED: Sepsis induces the release of lipid mediators, which control both lipid metabolism and inflammation. However, the role of serum apolipoprotein A-V (ApoA5) in sepsis is poorly understood in pediatric patients.
    UNASSIGNED: ApoA5 was screened from serum proteomics profile in lipopolysaccharide- (LPS-) treated mice for 2 h, 24 h, and controls. Then, we conducted a prospective pilot study, and patients with sepsis admitted to a pediatric intensive care unit (PICU) were enrolled from January 2018 to December 2018. Serum ApoA5 levels on PICU admission were determined using enzyme-linked immunosorbent assays (ELISA). Blood samples from 30 healthy children were used as control. The correlation of ApoA5 with the clinical and laboratory parameters was analyzed. Logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to investigate the potential role of serum ApoA5 as a prognostic predictor for PICU mortality in pediatric patients with sepsis.
    UNASSIGNED: A total of 101 patients with sepsis were enrolled in this study. The PICU mortality rate was 10.9% (11/101). Serum ApoA5 levels on PICU admission were significantly lower in nonsurvivors with sepsis compared with survivors (P = 0.009). In subgroup analysis, serum levels of ApoA5 were significantly correlated with sepsis-associated multiple organ dysfunction syndrome (MODS) (P < 0.001), shock (P = 0.002), acute kidney injury (AKI) (P < 0.001), acute liver injury (ALI) (P = 0.002), and gastrointestinal (GI) dysfunction (P = 0.012), but not respiratory failure, brain injury, and pathogenic species (all P > 0.05). Correlation analyses revealed significant correlations of serum ApoA5 with Ca2+ concentration. Remarkably, the area under ROC curve (AUC) for serum ApoA5 levels on PICU admission was 0.789 for prediction of PICU mortality with a sensitivity of 75% and a specificity of 84.5% at a threshold value of 822 ng/mL.
    UNASSIGNED: Serum ApoA5 level is associated with sepsis-associated shock, AKI, ALI, GI dysfunction, or MODS in children. Moreover, the findings of the present study suggest a prognostic value of ApoA5 in children with sepsis, and lower serum ApoA5 than 822 ng/mL predicts worse outcome in pediatric sepsis.
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  • 文章类型: Journal Article
    血脂异常是长期使用抗逆转录病毒疗法(ART)的潜在并发症,也已知与遗传因素有关。在加纳接受ART治疗的HIV患者中,与血脂异常相关的宿主遗传变异尚未得到充分探索。该研究共有289名HIV感染患者接受了至少一年的稳定ART治疗。将空腹血液收集到EDTA管中用于脂质测量。根据NCEP-ATPIII标准,使用脂质谱来定义血脂异常。HIV感染的受试者分为两组;血脂异常(病例)(n=90;31.1%)和无血脂异常(对照组)(n=199;68.9%)。确定了四个候选单核苷酸多态性(SNP)基因(ABCA1-rs2066714,LDLR-rs6511720,APOA5-rs662799和DSCAML1-rs10892151)。使用PCR对研究参与者的分离的基因组DNA进行基因分型,然后进行多重连接检测反应(LDR)。具有rs6511720(T/T)的罕见纯合子等位基因的人群百分比,rs2066714(G/G),病例中rs10892151(T/T)和rs662799(G/G)占5.5%,14.4%,6.6%和10.0%,2.0%9.1%,在对照组中观察到6.5%和4.0%。病例和对照组之间APOA5(p=0.0357)和LDLR多态性(p=0.0387)的基因型患病率存在统计学上的显着差异。与APOA5多态性的AA基因型相比,具有罕见纯合子基因型的个体[aOR=2.38,95CI(1.06-6.54),p=0.004]与控制年龄后发生血脂异常的可能性增加显着相关,性别,治疗持续时间,CD4计数和BMI。此外,具有ABCA1(G/G)的罕见纯合基因型的个体[aOR=10.7(1.3-88.7),p=0.0280]和LDLR(rs6511720)G>T[aOR=61.2(7.6-493.4),p<0.0001)更可能有高水平的总胆固醇水平。我们的数据强调了加纳人群中暴露于ART的HIV患者中四个候选基因中SNP的存在及其与血脂异常的关联。尤其是APOA5-rs662799和LDLRrs6511720中的变体。这些发现提供了基线信息,需要在ART治疗的HIV患者中监测血脂异常的症状前策略。有必要进行纵向研究以验证完整数量的SNP及其与血脂异常的关联。
    Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex ligation detection reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06-6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3-88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6-493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and their associations with dyslipidemia.
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  • DOI:
    文章类型: Journal Article
    OBJECTIVE: To explore the association of rs662799 variants of Apolipoprotein A5 gene with metabolic syndrome in Pakistani population.
    METHODS: The case-control study was conducted at Pakistan Institute of Medical Sciences, Islamabad, Pakistan from 2014 to2016, and comprised subjects enrolled from the out-patient clinics. Groups were formed on the basis of preliminary screening for risk factors like obesity, insulin resistance, hypertension, dyslipidemia and fasting blood glucose levels. Met S was diagnosed based on the international diabetes federation criteria. Blood samples were collected for biochemical testing and deoxyribonucleic acid extraction. Genotyping of rs662799 was performed a the Genome Research Centre of the University of Hong Kong using Sequenom Mass ARRAY, iPLEX Gold technology. Data was analysed using SPSS 16and Plink software.
    RESULTS: :There were 712 subjects in two groups of 356(50%) each. The overall mean age was 41.59}7.18 years. There was a significant association of risk allele C of rs662799 with metabolic syndrome (p=0.002). The risk showed strong association with dyslipidaemia (p=0.03) and obesity (p=0.01) which are risk phenotypes of metabolic syndrome in age- and gender-adjusted model.
    CONCLUSIONS: The association of risk allele C of genetic variant rs662799 of Apolipoprotein A5 gene with dyslipidaemia and obesity may lead to the development of metabolic syndrome in the Pakistan adult population.
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  • 文章类型: Journal Article
    The goal of this study is to investigate the associations of apolipoprotein A5 (APOA5) polymorphisms with coronary artery disease (CAD) in a Chinese population.
    This case-control study included 710 subjects (355 patients with CAD and 355 controls) who were recruited from a cross-sectional study. Three single nucleotide polymorphisms (SNPs) rs662799 (-1131T>C), rs651821 (-3A>G) and rs2075291 (G185C) in APOA5 were selected and genotyped using the matrix-assisted laser desorption ioniasation time of flight mass spectrometry technology. The χ2 test and haplotype analysis were performed to analyse the associations between APOA5 SNPs and CAD using the SPSS V.22.0 software package and the online SNPStats program.
    APOA5 SNPs rs662799 and rs651821 exhibited significant differences in genotype and allele distributions between patients with CAD and control subjects. The SNP rs662799 was significantly correlated with an increased risk of CAD when a dominant model was considered. The SNP rs651821 was significantly correlated with an increased risk of CAD when a codominant model was considered. Moreover, the variant C alleles of rs662799 and the variant G alleles of the rs651821 polymorphism were significantly correlated with increased plasma triglyceride (TG) levels in the CAD group (all p<0.05). Additionally, a mediating effect of TG on the associations between the APOA5 rs662799 and rs651821 polymorphisms and CAD was observed.
    Based on these data, variants of the APOA5 gene are associated with CAD susceptibility and may modulate plasma TG levels among a Chinese population.
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  • 文章类型: Journal Article
    Genome-wide association studies have identified numerous variants associated with lipid levels; yet, the majority are located in non-coding regions with unclear mechanisms. In the Insulin Resistance Atherosclerosis Family Study (IRASFS), heritability estimates suggest a strong genetic basis: low-density lipoprotein (LDL, h2 = 0.50), high-density lipoprotein (HDL, h2 = 0.57), total cholesterol (TC, h2 = 0.53), and triglyceride (TG, h2 = 0.42) levels. Exome sequencing of 1,205 Mexican Americans (90 pedigrees) from the IRASFS identified 548,889 variants and association and linkage analyses with lipid levels were performed. One genome-wide significant signal was detected in APOA5 with TG (rs651821, PTG = 3.67 × 10-10, LODTG = 2.36, MAF = 14.2%). In addition, two correlated SNPs (r2 = 1.0) rs189547099 (PTG = 6.31 × 10-08, LODTG = 3.13, MAF = 0.50%) and chr4:157997598 (PTG = 6.31 × 10-08, LODTG = 3.13, MAF = 0.50%) reached exome-wide significance (P < 9.11 × 10-08). rs189547099 is an intronic SNP in FNIP2 and SNP chr4:157997598 is intronic in GLRB. Linkage analysis revealed 46 SNPs with a LOD > 3 with the strongest signal at rs1141070 (LODLDL = 4.30, PLDL = 0.33, MAF = 21.6%) in DFFB. A total of 53 nominally associated variants (P < 5.00 × 10-05, MAF ≥ 1.0%) were selected for replication in six Mexican-American cohorts (N = 3,280). The strongest signal observed was a synonymous variant (rs1160983, PLDL = 4.44 × 10-17, MAF = 2.7%) in TOMM40. Beyond primary findings, previously reported lipid loci were fine-mapped using exome sequencing in IRASFS. These results support that exome sequencing complements and extends insights into the genetics of lipid levels.
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  • 文章类型: Journal Article
    OBJECTIVE: This study aimed to test the association between APOA5 3\'-UTR variants (rs662799) and cardiometabolic traits in Koreans.
    METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained. APOA5 mRNA expression was also measured.
    RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports. In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes. Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [β = -2.048, P < 0.001; β = -2.199, P < 0.001] as well as elevation of circulating triglyceride levels [β = 0.053, P < 0.001; β = 0.066, P < 0.001] in both the KoGES-ASAS and KNHANES groups. In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = -0.277, P = 0.027) and circulating triglyceride level (r = -0.340, P = 0.006) but not significantly correlated with circulating HDL cholesterol level. On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms.
    CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES. The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.
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