Association of APOE genotype with lipid profiles and type 2 diabetes mellitus in a Korean population

Seo, Jung Yeon; Youn, Byeong Ju; Cheong, Hyun Sub; Shin, Hyoung Doo

doi:10.1007/s13258-021-01095-y

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…The TOMM40 - ApoE region was found to be positively related to T2DM in a recent multi-ethnic Genome-wide association study (GWAS) ( Cook & Morris, 2016 ), and this association was effectively replicated in various cohorts, including Asians ( Long et al, 2019 ; El-Lebedy, Raslan & Mohammed, 2016 ). Consistent with the current study, the genetic influences of ApoE polymorphisms and genotype on T2DM susceptibility and lipid profiles, which have been attributed to T2DM, were determined in the Korean population ( Seo et al., 2021 ). We searched the public DIAGRAM type 2 diabetes GWAS data and found that the SNP in the ApoE locus was significantly associated with T2DM in European ancestry, with rs429358 as the leading SNP ( p = 1.4 ×10 −10 , beta = 0.12, number of T2DM cases = 26,676, number of controls = 132,532) ( Fig.…”

Section: Discussionsupporting

confidence: 87%

“…Our study is the first to reveal ApoE genotypes related with lipids in patients with diabetes in an older Chinese community. However, there are some differences between our study and the Korean population, where none of the ApoE polymorphisms, alleles (genotype), or haplotypes were significantly associated with T2DM risk, but only with lipids ( Seo et al., 2021 ). This variation may be explained by genetic variations between populations or it may be related to our sample’s slightly larger size (743 patients with T2DM and 995 unaffected controls) compared to the Korean study population (352 patients with T2DM and 1,084 unaffected controls).…”

Section: Discussioncontrasting

confidence: 75%

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Association of ApoE gene polymorphisms with serum lipid levels and the risk of type 2 diabetes mellitus in the Chinese Han population of central China

Zeng

Wen

Huan

et al. 2023

PeerJ

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Background Apolipoprotein E (ApoE) is involved in lipid transformation and metabolism. Although some studies have examined the association between ApoE polymorphisms and the risk of type 2 diabetes mellitus (T2DM), the findings differ depending on the location and population. Methods A total of 1,738 participants, including 743 patients with T2DM and 995 controls without T2DM, were enrolled from central China, and ApoE polymorphisms, 388T > C (rs429358) and 526C > T (rs7412), were genotyped. The association between ApoE alleles and T2DM and blood lipid levels was analyzed. Logistic regression analysis was performed to evaluate the interactions between ApoE polymorphisms and various factors, such as age, sex, and prevalence of hypertension in patients with T2DM. Results The genotype ɛ3/ɛ4 and ɛ4 alleles of ApoE were associated with T2DM risk in the Chinese Han population in central China. Moreover, in patients with T2DM, participants in the E4 (ɛ3/ɛ4, ɛ4/ɛ4) group had significantly higher lipid profiles than those in the E3 (ɛ3/ɛ3) group, whereas participants in the E2 group (ɛ2/ɛ2, ɛ2/ɛ3) showed lower total cholesterol, low-density lipoprotein cholesterol, and ApoE-A1 levels than those in the E3 (ɛ3/ɛ3) group. The results from the current study may help in understanding ApoE polymorphisms and lipid profiles in the Chinese Han population.

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Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 75%

Association of ApoE gene polymorphisms with serum lipid levels and the risk of type 2 diabetes mellitus in the Chinese Han population of central China

Zeng

Wen

Huan

et al. 2023

PeerJ

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“…Previous studies have shown that rs429358 is linked to HDL-C, LDL-C, TC, and TG levels [ 48 ]. Indeed, rs429358 was correlated with TG levels in Korean type 2 diabetes patients [ 49 ] and with TG levels and metabolic syndrome in Korean subjects [ 50 ]. In addition, rs429358 has been linked to Alzheimer’s disease [ 51 ], dementia, and Parkinson’s disease.…”

Section: Discussionmentioning

confidence: 99%

Sex-related differences in single nucleotide polymorphisms associated with dyslipidemia in a Korean population

2022

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Background The prevalence of dyslipidemia has increased steadily in Korea, and the incidence of dyslipidemia differs by sex. In this study, we identified single nucleotide polymorphisms (SNPs) related to dyslipidemia in Korean cohorts through genome-wide association study (GWAS) analysis. Methods Genotyping was conducted to determine the genotypes of 72,298 participants and investigate genotypes for 7,079,946 SNPs. Sex, age, and BMI were set as covariates for GWAS, and significant SNPs were identified in the discovery and replication stages using logistic regression. Results GWAS of the entire cohort revealed a total of five significant SNPs: rs117026536 (LPL), rs651821 (APOA5), rs9804646 (APOA5), rs9926440 (CETP), and rs429358 (APOE). GWAS of the male subjects revealed a total of four significant SNPs. While rs9804646 (APOA5) and rs429358 (APOE) were significant for all the subjects, rs662799 (APOA5) and rs56156922 (CETP) were significant only for the male subjects. GWAS of the female subjects revealed two significant SNPs, rs651821 (APOA5) and rs9804646 (APOA5), both of which were significant in all the subjects. Conclusion This is the first study to identify sex-related differences in genetic polymorphisms in Korean populations with dyslipidemia. Further studies considering environmental variables will be needed to elucidate these sex-related genetic differences in dyslipidemia.

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“…A recent study conducted in 2021 on Indonesian T2D patients reported no association between TC, TG, and LDL-C levels with APOE polymorphisms, but showed that ε2 and ε4 carriers had lower levels of HDL-C (32). Other studies revealed that APOE polymorphisms were associated with serum lipid levels in healthy controls but not in T2D patients (33,34). A meta-analysis of 16 studies revealed an association of APOE polymorphisms with the levels of TC, TG, HDL-C, and LDL-C (35).…”

Section: Discussionmentioning

confidence: 99%

Association of DNA methylation and genetic variations of the APOE gene with the risk of diabetic dyslipidemia

Ereqat

Cauchi²,

Eweidat

et al. 2022

Biomed Rep

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Apolipoprotein E (APOE) is a key regulator of lipoprotein metabolism, and consequently, affects the plasma and tissue lipid contents. The aim of the present study was to investigate the parallel effects of APOE genetic variants and promoter methylation levels of six CpGs on the risk of diabetic dyslipidemia. A total of 204 Palestinian type 2 diabetes (T2D) patients (mean age ± SD: 62.7±10.2) were enrolled in the present study (n=96 with dyslipidemia and n=108 without dyslipidemia). Next generation sequencing was performed to analyze five single nucleotide polymorphisms: Two variants rs7412 and rs429358 that determine APOE ε alleles, and three variants in the promoter region (rs769446, rs449647, and rs405509). For all subjects, the most common genotype was ε3/ε3 (79.4%). No statistical differences were observed in the APOE ε polymorphisms and the three promoter variants among T2D patients with and without dyslipidemia (P>0.05). A comparison of lipid parameters between ε3/ε3 subjects and ε4 carriers in both groups revealed no significant differences in the mean values of LDL-C, HDL-C, TG, and TC levels (P>0.05). Six CpG sites in the APOE promoter on chromosome 19:44905755-44906078 were identified, and differential DNA methylation in these CpGs were observed between the study groups. Logistic regression analysis revealed a significant association of DNA methylation level at the six CpGs with an increased risk of diabetic dyslipidemia (odds ratio, 1.038; 95% confidence interval, 1.012-1.064; P=0.004). In conclusion, the present study revealed that DNA methylation levels in six CpGs in the APOE promoter region was associated with the risk of diabetic dyslipidemia independently of the APOE ε4 variant which could be a potential therapeutic target to reverse the methylation of the APOE promoter.

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Association of APOE genotype with lipid profiles and type 2 diabetes mellitus in a Korean population

Cited by 9 publications

References 47 publications

Association of ApoE gene polymorphisms with serum lipid levels and the risk of type 2 diabetes mellitus in the Chinese Han population of central China

Association of ApoE gene polymorphisms with serum lipid levels and the risk of type 2 diabetes mellitus in the Chinese Han population of central China

Sex-related differences in single nucleotide polymorphisms associated with dyslipidemia in a Korean population

Association of DNA methylation and genetic variations of the APOE gene with the risk of diabetic dyslipidemia

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