scholarly journals Haplotypes of the Mutated SIRT2 Promoter Contributing to Transcription Factor Binding and Type 2 Diabetes Susceptibility

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 569
Author(s):  
Xiao Zheng ◽  
Jiajun Li ◽  
Jie Sheng ◽  
Yang Dai ◽  
Yue Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Binding Sites ◽  
Haplotype Block ◽  
Glycated Hemoglobin ◽  
Causative Factor ◽  
Diabetes Susceptibility ◽  
Haplotype Combination ◽  
Therapy Assessment ◽  
Haplotype Block Structure

Genetic variability is an important causative factor for susceptibility and pathogenesis of type 2 diabetes (T2D). Histone deacetylase, sirtuin 2 (SIRT2), plays regulatory roles in glucose metabolism and insulin sensitivity. However, whether the SIRT2 variants or haplotypes contribute to T2D risk remain to be elucidated. In this study, we first detected three novel polymorphisms (P-MU1, P-MU2, and P-MU3) in the promoter of SIRT2 in the Chinese population. All pairwise sets of the three loci were strongly in linkage disequilibrium. Next, we constructed the haplotype block structure, and found H1-GGC and H2-CCA accounted for the most (total 91.8%) in T2D. The haplotype combination H1-H1-GGGGCC displayed a high risk for T2D (OR = 2.03, 95% CI = 1.12–3.72). By association analysis, we found the individuals carrying H1-H1-GGGGCC had significantly higher fasting plasma glucose and glycated hemoglobin. The haplotype H1-GGC presented a 6.74-fold higher promoter activity than H2-CCA, which was consistent with the correlation results. Furthermore, we clarified the mechanism whereby the C allele of both the P-MU1 and P-MU2 loci disrupted the signal transducer and activator of transcription 1 (STAT1) binding sites, leading to the attenuation of the SIRT2 transcription. Together, these data suggest that the linked haplotype GGC could be considered as a promising marker for T2D diagnosis and therapy assessment.

scholarly journals Role of Calpain-10 Gene Variants in Familial Type 2 Diabetes in Caucasians

2002 ◽  
Vol 87 (2) ◽  
pp. 650-654 ◽  
Author(s):  
Steven C. Elbein ◽  
Winston Chu ◽  
Qianfang Ren ◽  
Chris Hemphill ◽  
John Schay ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Diabetes Susceptibility ◽  
Haplotype Combination ◽  
Calpain 10

The calpain-10 gene (CAPN10) has been implicated in type 2 diabetes (T2DM) susceptibility by both linkage and association in a Hispanic population from Starr County Texas. Common intronic variants seem to alter CAPN10 mRNA levels and were associated with insulin resistance but not diabetes in Pima Indians. The role of these variants in Caucasian populations is less clear. We found some evidence for linkage of T2DM to chromosome 2q approximately 20 cM proximal to the NIDDM1/CAPN10 locus. To test the hypothesis that CAPN10 is a diabetes susceptibility locus in Caucasian families at high risk for T2DM, we examined the influence of the three previously implicated CAPN10 variants on both diabetes risk and measures of insulin sensitivity and glucose homeostasis. We genotyped approximately 700 members of 63 families for 3 variants (SNP-43, SNP-19, and SNP-63). We tested each variant separately and as haplotype combinations for altered transmission from parents to affected children (transmission disequilibrium test), and we tested for an effect of each variant individually on measures of glucose and insulin during a glucose tolerance test in nondiabetic family members. Finally, we looked for an effect of each variant on measures of insulin sensitivity (SI) and insulin secretion estimated by frequently sampled iv glucose tolerance test and Minimal Model analysis. We could not confirm an increase in risk for T2DM susceptibility for any variant or for any haplotype combination, although we found marginal evidence for an increased risk of the 111/221 haplotype combination (P = 0.036) after ascertainment correction. However, both SNP-19 and SNP-63 increased fasting and/or postchallenge insulin levels, consistent with reduced insulin sensitivity. Furthermore, SNP-19 had modest effects on insulin sensitivity measured by homeostatic model, and on postchallenge glucose. The reduction in insulin sensitivity was confirmed by analysis of the subset of individuals who underwent iv glucose tolerance tests, where SNP-19 significantly altered the insulin sensitivity index. CAPN10 cannot be considered a major diabetes susceptibility gene in our population and seems unlikely to explain the observed linkage findings. However, CAPN10 influences insulin sensitivity and glucose homeostasis in nondiabetic members of kindreds at high risk for T2DM.

25-OR: Investigating a Candidate Causal Allele in Type 2 Diabetes Susceptibility Gene PAM as a Cause of Neonatal Diabetes Mellitus

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 25-OR
Author(s):  
SHAHANA SENGUPTA ◽  
LORI L. BONNYCASTLE ◽  
BENOIT HASTOY ◽  
ANTJE GROTZ ◽  
MAHESH M. UMAPATHYSIVAM ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Susceptibility Gene ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Diabetes Susceptibility ◽  
Diabetes Susceptibility Gene ◽  
Causal Allele

304-OR: Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
MICHAEL L. MULTHAUP ◽  
RYOSUKE KITA ◽  
NICHOLAS ERIKSSON ◽  
STELLA ASLIBEKYAN ◽  
JANIE SHELTON ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Diabetes Susceptibility ◽  
Genetic Database ◽  
Polygenic Risk

scholarly journals Glycemic variability and cardiovascular disease in patients with type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002032
Author(s):  
Marcela Martinez ◽  
Jimena Santamarina ◽  
Adrian Pavesi ◽  
Carla Musso ◽  
Guillermo E Umpierrez
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycated Hemoglobin ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Cardiovascular Complications ◽  
Glucose Levels ◽  
Increased Risk ◽  
Patients With Diabetes

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

Fasting and post-prandial glycemia and their correlation with glycated hemoglobin in Type 2 diabetes

2006 ◽  
Vol 29 (7) ◽  
pp. 619-624 ◽  
Author(s):  
M. Monami ◽  
C. Lamanna ◽  
L. Lambertucci ◽  
R. Longo ◽  
C. Cocca ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycated Hemoglobin
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