scholarly journals Genetic Variants Associated with the Development of Type 2 Diabetes: Approaches to Their Identification

2019 ◽  
Vol 74 (1) ◽  
pp. 44-53
Author(s):  
Alexandra V. Stepanova ◽  
Konstantin Y. Kulebyakin ◽  
Tatyana N. Kochegura ◽  
Marina V. Shestakova ◽  
Vsevolod A. Tkachuk
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Variants ◽  
Main Type ◽  
Special Focus ◽  
Nucleotide Polymorphisms ◽  
Future Prospects ◽  
Single Nucleotide ◽  
Modern Methods

In the development of type 2 diabetes (T2D), an important role is played by a combination of environmental factors (hypodynamia, hypernutrition, etc.) and genetic variants that predispose the development of the disease. The contribution of inherited traits to the development of T2D can reach 80%, which is confirmed by the results of a number of published studies. At the same time, the multifactorial and polygenetic nature of T2D makes it difficult to establish direct cause-effect relations between individual genetic variants and specific metabolic changes. This explains a large number of studies and a long ongoing search for the most convenient and effective strategy for assessing the role of single nucleotide polymorphisms (SNP), the main type of genetic variation in the human genome. Involvement of specialists from various fields and the emergence of many methods for processing and interpreting data have led to the parallel development of scientific approaches. In this review of the main approaches (except mathematical ones) their characteristics will be described and the results obtained with their help will be evaluated, with special focus on new features of modern methods of genome editing, in particular the CRISPR/Cas9 system, and the future prospects in this area.

scholarly journals SNP rs2073618 of the Osteoprotegerin Gene Is Associated with Diabetic Retinopathy in Slovenian Patients with Type 2 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Sara Mankoč Ramuš ◽  
Tina Kumše ◽  
Mojca Globočnik Petrovič ◽  
Daniel Petrovič ◽  
Ines Cilenšek
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Strong Association ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Regulatory Molecule ◽  
Codominant Model ◽  
Osteoprotegerin Gene

Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26–5.13, ). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR.

scholarly journals Association between ABC family variants rs1800977, rs4149313, and rs1128503 and susceptibility to type 2 diabetes in a Chinese Han population

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094134
Author(s):  
Ruicheng Yan ◽  
Jianfei Luo ◽  
Xiaobo He ◽  
Shijun Li
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Variants ◽  
Recessive Model ◽  
Genetic Models ◽  
Chinese Han Population ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Han Population

Objective To investigate the association between three single nucleotide polymorphisms (SNPs) of the ATP-binding cassette (ABC) gene family and susceptibility to type 2 diabetes mellitus in a Chinese Han population. Methods A total of 1086 type 2 diabetes patients and 1122 healthy controls were included in this retrospective study. Three genetic variants, rs1800977 and rs4149313 in ABCA1, and rs1128503 in ABCB1 were included in the study. Susceptibility to type 2 diabetes was evaluated under three genetic models. Results A significant association between rs1800977 and type 2 diabetes was identified in three different genetic models (TT vs CC, odds ratio [OR] = 0.611 [95% confidence interval (CI), 0.469–0.798]; T vs C, OR = 0.841 [95% CI, 0.745–0.950]; and the recessive model, OR = 0.606 [95% CI, 0.474–0.774]). Additionally, a significant association between rs4149313 and type 2 diabetes was identified in three different genetic models (AA vs GG, OR = 0.467 [95% CI, 0.326–0.670]; A vs G, OR = 0.819 [95% CI, 0.717–0.935]; and the recessive model, OR = 0.478 [95% CI, 0.336–0.680]). Conclusion We found that SNPs rs1800977 and rs4149313 in ABCA1 are significantly associated with susceptibility to type 2 diabetes in a Chinese population, although this should be confirmed in a larger study.

scholarly journals Discovery of Coding Genetic Variants Influencing Diabetes-Related Serum Biomarkers and Their Impact on Risk of Type 2 Diabetes

2015 ◽  
Vol 100 (4) ◽  
pp. E664-E671 ◽  
Author(s):  
Tarunveer Singh Ahluwalia ◽  
Kristine Højgaard Allin ◽  
Camilla Helene Sandholt ◽  
Thomas Hempel Sparsø ◽  
Marit Eika Jørgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Heat Shock ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Variants ◽  
Binding Protein ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Igf Binding ◽  
Igf Binding Protein

Context: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease. Objective: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin. Design and Participants: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls. Results: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10−7. Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously. Conclusion: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.

scholarly journals AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia: Studies of Metabolic Traits in 7,683 White Danish Subjects

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1427-1432 ◽  
Author(s):  
G. Andersen ◽  
K. S. Burgdorf ◽  
T. Sparso ◽  
K. Borch-Johnsen ◽  
T. Jorgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Metabolic Traits

scholarly journals Type 2 Diabetes (T2D) Associated Polymorphisms Regulate Expression of Adjacent Transcripts in Transformed Lymphocytes, Adipose, and Muscle from Caucasian and African-American Subjects

2011 ◽  
Vol 96 (2) ◽  
pp. E394-E403 ◽  
Author(s):  
Neeraj K. Sharma ◽  
Kurt A. Langberg ◽  
Ashis K. Mondal ◽  
Steven C. Elbein ◽  
Swapan K. Das
Keyword(s):  
Genome Wide Association ◽  
Small Subset ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Allelic Expression Imbalance ◽  
Single Nucleotide ◽  
Metabolic Traits ◽  
Genome Wide

abstract Context: Genome-wide association scans (GWAS) have identified novel single nucleotide polymorphisms (SNPs) that increase T2D susceptibility and indicated the role of nearby genes in T2D pathogenesis. Objective: We hypothesized that T2D-associated SNPs act as cis-regulators of nearby genes in human tissues and that expression of these transcripts may correlate with metabolic traits, including insulin sensitivity (SI). Design, Settings, and Patients: Association of SNPs with the expression of their nearest transcripts was tested in adipose and muscle from 168 healthy individuals who spanned a broad range of SI and body mass index (BMI) and in transformed lymphocytes (TLs). We tested correlations between the expression of these transcripts in adipose and muscle with metabolic traits. Utilizing allelic expression imbalance (AEI) analysis we examined the presence of other cis-regulators for those transcripts in TLs. Results: SNP rs9472138 was significantly (P = 0.037) associated with the expression of VEGFA in TLs while rs6698181 was detected as a cis-regulator for the PKN2 in muscle (P = 0.00027) and adipose (P = 0.018). Significant association was also observed for rs17036101 (P = 0.001) with expression of SYN2 in adipose of Caucasians. Among 19 GWAS-implicated transcripts, expression of VEGFA in adipose was correlated with BMI (r = −0.305) and SI (r = 0.230). Although only a minority of the T2D-associated SNPs were validated as cis-eQTLs for nearby transcripts, AEI analysis indicated presence of other cis-regulatory polymorphisms in 54% of these transcripts. Conclusions: Our study suggests that a small subset of GWAS-identified SNPs may increase T2D susceptibility by modulating expression of nearby transcripts in adipose or muscle.

scholarly journals Coffee Consumption, Genetic Polymorphisms, and the Risk of Type 2 Diabetes Mellitus: A Pooled Analysis of Four Prospective Cohort Studies

2020 ◽  
Vol 17 (15) ◽  
pp. 5379
Author(s):  
An Na Kim ◽  
Hyun Jeong Cho ◽  
Jiyoung Youn ◽  
Taiyue Jin ◽  
Moonil Kang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Regression Models ◽  
Coffee Consumption ◽  
Pooled Analysis ◽  
Random Effects Model ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Logistic Regression Models

The association between coffee consumption and the risk of type 2 diabetes may vary by genetic variants. Our study addresses the question of whether the incidence of type 2 diabetes is related to the consumption of coffee and whether this relationship is modified by polymorphisms related to type 2 diabetes. We performed a pooled analysis of four Korean prospective studies that included 71,527 participants; median follow-up periods ranged between 2 and 13 years. All participants had completed a validated food-frequency questionnaire (FFQ) at baseline. The odds ratios (ORs) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using logistic regression models. The ORs were combined using a fixed or random effects model depending on the heterogeneity across the studies. Compared with 0 to <0.5 cups/day of coffee consumption, the OR for type 2 diabetes was 0.89 (95% CI: 0.80–0.98, p for trend = 0.01) for ≥3 cups/day of coffee consumption. We did not observe significant interactions by five single nucleotide polymorphisms (SNPs) related to type 2 diabetes (CDKAL1 rs7756992, CDKN2A/B rs10811661, KCNJ11 rs5215, KCNQ1 rs163184, and PEPD rs3786897) in the association between coffee and the risk of type 2 diabetes. We found that coffee consumption was inversely associated with the risk of type 2 diabetes.

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