Association study of genetic polymorphisms of SLC2A10 gene and type 2 diabetes in the Taiwanese population

Abstract Epigenetics alternation of non-genetic variation and genome-wide association study proven allelic variants may associate with insulin secretion in type 2 diabetes (T2D) development. We analyzed promoter DNA methylation array to evaluate the associated with increased susceptibility to T2D (30 cases, 10 controls) and found 1,091 gene hypermethylated in promoter regions. We performed the association study of T2D and found 698 single nucleotide polymorphisms in exon and promoter sites by using 2,270 subjects (560 cases, 1,710 controls). A comparison of DNA hypermethylation and gene silencing of mouse T2D results in our T2D patients’ results showed that the 5′-nucleotidase, cytosolic II (NT5C2) and fucosyltransferase 8 (FUT8) genes were strongly associated with increased susceptibility to T2D. DNA hypermethylation in promoter regions reduced NT5C2 gene expression, but not FUT8 in T2D patients. NT5C2 protein expression was decreased in pancreatic β-cells from T2D mice. Transient transfection NT5C2 into RIN-m5F cells down-regulated DNA methyltransferase I (DNMT1) expression and up-regulation of the insulin receptor. Moreover, NT5C2 knockdown induced in DNMT1 overexpression and insulin receptor inhibition. Taken together, these results showed that NT5C2 epigenetically regulated insulin receptor in patients and mice with T2D, and maybe provide for T2D therapy strategy.

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Association of Alcohol Drinking With Incident Type 2 Diabetes and Pre-diabetes: the Guangzhou Biobank Cohort Study

10.21203/rs.3.rs-955149/v1 ◽

2021 ◽

Author(s):

Mei Jiao Li ◽

Jing Ren ◽

Wei Sen Zhang ◽

Chao Qiang Jiang ◽

Ya Li Jin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Polymorphisms ◽

Impaired Fasting Glucose ◽

Alcohol Drinking ◽

Fasting Glucose ◽

Heavy Alcohol ◽

Incident Type ◽

Incident Type 2 Diabetes

Abstract Background To examine associations of baseline alcohol drinking with incident type 2 diabetes or impaired fasting glucose, and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B).Methods Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident type 2 diabetes was defined as fasting glucose ≥7.0 mmol/l or post-load glucose ≥11.1 mmol/l at follow-up examination (2008-2012), self-reported type 2 diabetes and/or initiation of hypoglycemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/l and <7 mmol/l. Results Of 15,716 participants without diabetes and 11,232 participants without diabetes and impaired fasting glucose at baseline, 1,624 (10.33%) developed incident type 2 diabetes, and 1,004 (8.94%) developed incident impaired fasting glucose during average 4 years of follow-up. After adjusting for sex, age, education, occupation, personal annual income, smoking, physical activity, body mass index, waist/hip ratio, health status, family history of diabetes, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident type 2 diabetes+impaired fasting glucose (odds ratio (OR) 1.08, 95% confidence interval (CI) 0.94-1.25, and 0.89 (0.68-1.16), respectively), but heavy alcohol drinking was associated with a higher risk of incident type 2 diabetes+impaired fasting glucose (1.83, 1.25-2.69). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B or ALDH2 genes with alcohol drinking on incident type 2 diabetes and/or impaired fasting glucose were found (p for interaction from 0.12 to 0.81). Conclusions Our results support a detrimental effect of heavy alcohol use on impaired fasting glucose and type 2 diabetes. No protective effect was found for those carrying lower risk alleles for ADH1B and ALDH2 genes.

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Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults

Nutrients ◽

10.3390/nu14020362 ◽

2022 ◽

Vol 14 (2) ◽

pp. 362

Author(s):

Xiaoting Lu ◽

Rongzhu Huang ◽

Shuyi Li ◽

Aiping Fang ◽

Yuming Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Polymorphisms ◽

Lower Risk ◽

Methylenetetrahydrofolate Reductase ◽

Community Dwelling ◽

Cox Proportional Hazards Model ◽

Chinese Adults ◽

Baseline Serum ◽

Mthfr A1298c

Previous studies have explored associations between betaine and diabetes, but few have considered the effects of genes on them. We aimed to examine associations between serum betaine, methyl-metabolizing genetic polymorphisms and the risk of type 2 diabetes in Chinese adults. This prospective study comprised 1565 subjects aged 40–75 without type 2 diabetes at baseline. Serum betaine was measured by high-performance liquid chromatography tandem mass spectrometry. Genotyping of methyl-metabolizing genes was detected by Illumina ASA-750K arrays. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median of 8.9 years of follow-up, 213 participants developed type 2 diabetes. Compared with participants in the lowest quartile of serum betaine, those in the highest quartile had lower risk of type 2 diabetes, adjusted HRs (95%CIs) was 0.46 (0.31, 0.69). For methylenetetrahydrofolate reductase (MTHFR) G1793A (rs2274976) and MTHFR A1298C (rs1801131), participants carrying 1793GA + AA and 1298AC + CC had lower risk of type 2 diabetes. Interactions of serum betaine and genotype of MTHFR G1793A and MTHFR A1298C could be found influencing type 2 diabetes risk. Our findings indicate that higher serum betaine, mutations of MTHFR G1793A and A1298C, as well as the joint effects of them, are associated with lower risk of type 2 diabetes.

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Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

10.1101/2021.03.23.436581 ◽

2021 ◽

Author(s):

Samantha Streicher ◽

Unhee Lim ◽

S. Lani Park ◽

Yuqing Li ◽

Xin Sheng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

European Ancestry ◽

American Population ◽

Pancreatic Fat ◽

Genome Wide ◽

Multiethnic Cohort

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10 -8 ) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10 -8 ) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also suggestively associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUT , and rs79967607 is in intron 1 of EPM2A . PLUT, a linkRNA, regulates transcription of an adjacent gene, PDX1 , that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.

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