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The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans.

ABSTRACT: The role of angiopoietin-like 3 (ANGPTL3) in blood lipid levels, cardiovascular disease risk, and glucose metabolism has received wide attention. This study aimed to examine whether rs11207997 in ANGPTL3 is associated with a 10-year risk of diabetes mellitus (DM) and if the association is modified by the consumption of certain food groups or nutrients. A prospective cohort study was designed using the Ansan-Ansung data of the Korean Genome and Epidemiology Study (n?=?7,358; age ?40 years at baseline). Participants with the T allele of rs11207997, particularly TT homozygotes, had lower triglyceride (TG) and total cholesterol levels than those with CC. There was no association with fasting blood glucose or other biochemical parameters. ANGPTL3 mRNA was positively associated with circulating TG levels and blood pressure (all p?

SUBMITTER: Park CY

PROVIDER: S-EPMC6347602 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans.

Park Clara Yongjoo CY Moon Jiyoung J Jo Garam G Lee Juhee J Kim Oh Yoen OY Oh Hannah H Lim Hyunjung H Shin Min-Jeong MJ

Scientific reports 20190125 1

The role of angiopoietin-like 3 (ANGPTL3) in blood lipid levels, cardiovascular disease risk, and glucose metabolism has received wide attention. This study aimed to examine whether rs11207997 in ANGPTL3 is associated with a 10-year risk of diabetes mellitus (DM) and if the association is modified by the consumption of certain food groups or nutrients. A prospective cohort study was designed using the Ansan-Ansung data of the Korean Genome and Epidemiology Study (n = 7,358; age ≥40 years at base ...[more]

PMID: 30683883

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Project description:SIRT1 has been demonstrated in nutrient-sensing and insulin-signaling pathways in in vivo and in vitro experiments, but there is minimal information concerning the association between gene polymorphisms of SIRT1 and type 2 diabetes mellitus (T2DM) in a Chinese Han population. Using case-control design, we recruited 310 unrelated T2DM patients from inpatients at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, while 301 healthy controls were volunteers from the community for regular medical checkup. All participants were genotyped within the SIRT1 region. The following five SNPs rs10509291, rs12778366, rs10997870, rs10823112, and rs4746720 cover 100% of common genetic variations (minor allele frequency≥0.05) within the SIRT1 gene (r2≥0.8). The genotypes of SIRT1 gene polymorphisms were analyzed by the Snapshot assay and DNA sequencing. The resulting data show that there was significant genetic differentiation in rs10823112 [p=0.003; OR (95% CI)=1.515 (1.152-1.994) for genotype], rs4746720 [p=0.024; OR (95% CI)=1.37 (1.037-1.674) for genotype], and rs10509291 [p=0.002; OR (95% CI)=1.551 (1.179-2.04) for genotype] between T2DM and control subjects. However, the result of rs4746720 was no longer significant after correction for multiple testing (p after Bonferroni correction=0.12); the results of rs10509291and rs10823112 were still significantly different between the two groups (p after Bonferroni correction=0.01 and 0.015, respectively). Linear regression analyses adjusting for age, gender, and body mass index (BMI) showed that HbA1c and HOMA-IR in subjects with rs10509291 AA genotype were higher than those with TT genotype in T2DM group (p=0.045, p=0.035, respectively). Together, our data show that genetic variation of the SIRT1 gene is related to insulin resistance and increase risk of T2DM in Chinese Han population. The risk allele A at SIRT1 rs10509291 was closely associated with T2DM, and subjects who were homozygous of the A allele were more likely to develop T2DM.

Project description:We will explore the genetic (including APC, k-ras, p53, MSI, etc.) and environmental (including family history, life style, diet, nutritional status, DM, serum IGF-I, IGFBP-3, etc.) risk factors of colorectal tumorigenesis. We will accrue approximately 1000 patients as experimental group. The control group consists of 2000 individuals who were confirmed without colorectal cancer or polyps by colonoscopy. We estimated the statistical power of this study will reach more than 90%. In the second year, we will explore the association between various environmental risk factors with the epigenetic changes of various oncogenes and tumor suppressor genes. Firstly, we will study the correlation between hypermethylation of promoter region of hMLH1 gene with various environmental factors. Next, we will explore the genetic polymorphisms of promoter of E-cadherin gene. Recently, it has been reported that the C→A genetic polymorphism in the promoter region of E-cadherin gene in prostate cancer. Since this phenomenon has not been reported in colorectal cancer, it is mandatory for us to extend our research to the E-cadherin polymorphisms of colorectal cancer. Moreover, this project will focus on exploration of the association between the genetic polymorphisms of promoter of TS gene with chemosensitivity to 5-Fu-based therapy. We speculated that the better prognosis in colorectal tumors with MSI is related to their expression of TS gene. In summary, the second year of this project will extend our accumulated experience in the study of genetic polymorphisms to further clarify the association between genetic polymorphisms of TS gene with the prognosis of colorectal cancers after chemotherapy. We believe that this project will facilitate: (1) the further clarification of colorectal cancer tumorigenesis; (2) the establishment of domestic epidemiological data of colorectal cancer of Taiwan, and (3) the improvement of the quality of clinical management of patients with colorectal cancer.

Dataset Information

The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans.

Publications

The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans.

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