The c.553G&gt;T Genetic Variant of the<i>APOA5</i>Gene and Altered Triglyceride Levels in the Asian Population: A Meta-Analysis of Case–Control Studies

He, Hongbin; Lei, Lei; Chen, Erfei; Dong, Jing; Zhang, Kejin

doi:10.1089/gtmb.2016.0047

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…The present findings of associations of the APOA5 -1131T>C and c.553G>T polymorphisms with higher TG levels and lower HDL cholesterol levels are highly consistent with the results of meta-analyses reported by Zhao et al [ 23 ] and He et al [ 11 ], respectively. The apoA5 protein encoded by the APOA5 gene is a well-known apolipoprotein and an important determinant of plasma TG levels, which are a major risk factor for CAD [ 3 ].…”

Section: Discussionsupporting

confidence: 93%

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A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients

et al. 2017

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Hypertriglyceridemia is recognized as an independent risk factor for coronary artery disease. The apolipoprotein A5 gene (APOA5) is a key regulator of triglyceride levels. We aimed to evaluate the associations of single nucleotide polymorphisms (SNPs) in APOA5, including -1131T>C and c.553G>T, with hypertriglyceridemia, apoA5 concentrations, atherogenic LDL cholesterol levels, and arterial stiffness in hypertriglyceridemic patients. The study population included 599 hypertriglyceridemic patients (case) and 1,549 untreated normotriglyceridemic subjects (control). We genotyped two APOA5 variants, -1131T>C (rs662799) and c.553G>T (rs2075291). The frequencies of the CC genotype of -1131T>C (0.165) and the T allele of c.553G>T (0.119) were significantly higher in hypertriglyceridemic patients than in normotriglyceridemic subjects (0.061 and 0.070, respectively; all p<0.001). In the control and case groups, both the -1131T>C and c.553G>T variants were associated with higher triglyceride and lower HDL cholesterol levels. Controls with the -1131CC variant had lower apoA5 concentrations than controls with the -1131TT variant. Similar effects of the -1131T>C variant on apoA5 were observed in the cases. In the hypertriglyceridemic group, the -1131T>C variant was associated with a smaller LDL particle size, higher levels of oxidized LDL and malondialdehyde, and higher brachial-ankle pulse wave velocity. The -1131T>C and c.553G>T polymorphisms were associated with hypertriglyceridemia in the study population, but only the -1131T>C polymorphism directly affected apoA5 concentrations. Hypertriglyceridemic patients carrying the APOA5 -1131T>C polymorphism exhibited increased atherogenic LDL levels and arterial stiffness, probably due to an effect of the -1131T>C polymorphism on apoA5 concentrations.

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Section: Discussionsupporting

confidence: 93%

“…Both apolipoprotein A5 (apoA5) and APOA5 are key regulators of plasma triglyceride (TG) levels [ 8 – 11 ]. In many human populations, APOA5 SNPs are associated with variations in serum TG levels.…”

Section: Introductionmentioning

confidence: 99%

A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients

et al. 2017

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“…The associations of both the APOA5 rs662799 and rs2075291 SNPs with lower HDL‐cholesterol levels and higher triglyceride levels may be supported by the meta‐analyses of Zhao and Zhao and He et al, respectively. In addition, APOA5 rs662799 C allele carriers had higher TG and lower HDL‐cholesterol than the TT homozygotes carriers in 1840 Chinese participants .…”

Section: Discussionsupporting

confidence: 92%

Apolipoprotein A5 gene variants are associated with decreased adiponectin levels and increased arterial stiffness in subjects with low high‐density lipoprotein‐cholesterol levels

Kim

Yoo

et al. 2018

Clinical Genetics

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We performed a genome-wide association study to find genetic variants associated with high-density lipoprotein (HDL)-cholesterol levels in a Korean population and verified two apolipoprotein A5 (APOA5) gene variants, rs662799 (-1131T>C) and rs2075291 (c.553G>T), in 612 subjects with low HDL-cholesterol (cases) and 1536 subjects with normal HDL-cholesterol (controls). To explain this association, we compared clinical outcomes according to their genotype in normal (control) and low HDL (case) groups. In both the case and control groups, the rare alleles of rs662799 and rs2075291 were associated with higher triglyceride and lower HDL-cholesterol levels. In the subjects with the rs662799 CC genotype, lower levels of apoA-I and apoA-V and a smaller low-density lipoprotein (LDL) particle size were detected in both the case and control groups. In the case group, APOA5 rs662799 single nucleotide polymorphisms (SNPs) were associated with lower adiponectin and higher brachial-ankle pulse wave velocity (ba-PWV). Our results show that two APOA5 variants, rs662799 (-1131T>C) and rs2075291 (c.553G>T), are associated with HDL-cholesterol levels in a Korean population, and suggest that individuals with an APOA5 rs662799 CC genotype are at higher risk of atherosclerosis, particularly when they have low HDL-cholesterol, and this association is related to adiponectin levels.

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“…In line with this evidence, the G > T substitution at rs2075291 is also predicted to have a deleterious effect on apoAV functions by PolyPhen-2 and PROVEAN. Rs2075291 is associated with elevated TG levels 12 – 17 , 40 and lower HDL-C levels 18 in other Asian populations as well as in our datasets.…”

Section: Discussionsupporting

confidence: 65%

Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia

Han

Dorajoo

Chang

et al. 2017

Sci Rep

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Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10−8) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10−10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10−7–0.047). Seven pathways (P: 1.10 × 10−5–0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.

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The c.553G>T Genetic Variant of theAPOA5Gene and Altered Triglyceride Levels in the Asian Population: A Meta-Analysis of Case–Control Studies

Abstract: Our results suggest that APOA5 c. 553T is an independent risk factor for HTG and increased triglyceride levels in the Asian population. APOA5 c. 553T could be employed as a genetic risk marker for HTG and increased triglyceride levels.

Cited by 10 publications

References 42 publications

A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients

A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients

Apolipoprotein A5 gene variants are associated with decreased adiponectin levels and increased arterial stiffness in subjects with low high‐density lipoprotein‐cholesterol levels

Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia

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