scholarly journals Association of FTO gene variant (rs8050136) with type 2 diabetes and markers of obesity, glycaemic control and inflammation

2019 ◽  
Vol 38 (2) ◽  
pp. 153-163 ◽  
Author(s):  
Tamer Bego ◽  
Adlija Čaušević ◽  
Tanja Dujić ◽  
Maja Malenica ◽  
Zelija Velija-Asimi ◽  
...  

Summary Background FTO, a gene recently discovered in genomewide associated studies for type 2 diabetes mellitus (T2D), play an important role in the management of energy homeostasis, nucleic acid demethylation and regulation of body fat mass by lipolysis. The aim of this study was to analyze the association of FTO rs8050136 A>C genetic variant with clinical and biochemical parameters of T2D in the population of West Balkan region (Bosnians and Herzegovinians and Kosovars). Methods The study included 638 patients with T2D and prediabetes and 360 healthy controls of both genders, aged from 40 to 65 years. Patients were recruited at the Clinical Centre University of Sarajevo, University Hospital of Clinical Centre in Banja Luka, General Hospital in Tešanj and Health Centre in Prizren. Genotyping of analyzed FTO polymorphism rs8050136 A>C was performed by qPCR allelic discrimination. Results Genotype frequencies of the analyzed polymorphism were comparable between patients with T2D, prediabetic patients, and healthy population. Logistic regression analyses didn’t show significant association of FTO rs8050136 A allele with increased risk of T2D. However, risk A allele was significantly associated with higher levels of HbA1c, insulin, HOMA-IR index, diastolic blood pressure, and inflammatory markers (fibrinogen and leukocytes) as well as showed tendency of association with increased values of obesity markers (BMI, waist and hip circumference). Conclusions Results of our study showed a significant association of FTO genetic variant rs8050136 A>C with the major markers of insulin resistance, obesity and inflammation, opening new avenues for solving many unclear questions in the pathogenesis of T2D.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mai Ichikawa ◽  
Tadashi Konoshita ◽  
Yasukazu Makino ◽  
Jinya Suzuki ◽  
Tamotsu Ishizuka ◽  
...  

Abstract The renin-angiotensin system (RAS) is important in the onset and course of cardiovascular, kidney, and metabolic disorders. Previous reports showed that the RAS blockade protects organs and suppress the development of type 2 diabetes mellitus. A novel component of the RAS, namely, chromosome 9 open reading frame 3 (C9orf3), was recently identified, however, its effects are unclear. We evaluated whether the genetic variant of C9orf3 is associated with morbidity of hypertension among subjects with type 2 diabetes. We enrolled 382 subjects with type 2 diabetes, 222 of whom were diagnosed with hypertension. Human leukocyte genomic DNA was isolated and a genetic variant was analyzed for a C/T variant of C9orf3 (rs4385527) via PCR analysis. The relationship between the genotype and hypertension morbidity among subjects with diabetes was examined. The proportion of the respective C9orf3 genetic variants were as follows 247 CC, 119 CT, and 16 TT. The risk of hypertension was determined to be 1.58, with a 95% confidence interval of 1.11–2.27. Moreover, the p value was 0.012 for allelic comparison and for Armitage’s trend test, with the C allele identified as the risk factor. Consequently, hypertension was markedly associated with type 2 diabetes in subjects with the C9orf3 variant, exhibiting a nearly 1.6-fold increased risk. The C variant of a new component of the RAS, C9orf3 (rs4385527) might have a considerable impact on the pathogenesis of hypertension in diabetes.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yacob Pinchevsky ◽  
Neil Butkow ◽  
Tobias Chirwa ◽  
Frederick Raal

Aims. The management of cardiometabolic goals or “ABCs” (HbA1c, blood pressure (BP), and cholesterol) ultimately determines the morbidity and mortality outcomes in patients with type 2 diabetes mellitus (T2DM). We sought to determine if patients with T2DM attending an urbanized public sector community health centre (CHC) were having their ABCs measured, were treated with appropriate cardioprotective agents and finally, were achieving guideline-based targets. Methods and Results. A cross-sectional record review of 519 patients was conducted between May and August 2015. The mean age was 54 years (SD: ±11.5) and 54% (n=280) were females. Testing of ABCs occurred in 68.8% (n=357) for HbA1c, 95.4% (n=495) for BP, and 58.6% (n=304) for LDL-C. Achievement of ABC targets was as follows: 19.3% (HbA1c < 7%), 22.0% (BP < 140/80 mmHg), and 56.3% (LDL-C < 2.5 mmol/l). Conclusion. There were a significant number of patients who were not tested nor received adequate pharmacotherapy or achieved their ABC targets. This places these patients at an increased risk for the development of diabetes-related complications. Although the realities of resource constraints exist in South Africa’s public sector settings, a wider implementation of evidence-based guidelines must be instituted in order to ensure better patient outcomes.


2021 ◽  
Vol 10 (22) ◽  
pp. 5407
Author(s):  
Monika Buraczynska ◽  
Izabela Zakrocka

Studies have demonstrated that polymorphic variants of arginase 1 gene (ARG1) are involved in human diseases, such as coronary heart disease, hypertension, and diabetes. Our study aimed to investigate the association between ARG1 rs2781666 single nucleotide polymorphism (SNP) and diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients. Polymorphism was genotyped in 740 T2DM patients and 400 healthy individuals. A significant difference in the genotype distribution was observed between the patients and the controls. The T allele and TT genotype were associated with an increased risk of T2DM (OR 1.4, 95% CI 1.14–1.72, p = 0.001 and OR 2.16, 95% CI1.23–3.80, p = 0.007, respectively). When the T2DM subjects were stratified into DR+ and DR− subgroups, the T allele and TT genotype frequencies were significantly higher in the DR+ group compared to the DR− group, demonstrating OR 1.68 (1.33–2.12), p < 0.0001 and OR 2.39 (1.36–4.18), p = 0.002, respectively. Logistic regression analysis was applied to determine the interaction between the ARG1 genotypes and other risk factors. Only ARG1 rs2781666 SNP was a significant risk predictor of DR (p = 0.003). In conclusion, this is the first report discussing the effect of ARG1 polymorphism on the microvascular complications that are associated with diabetes. Our findings demonstrate that ARG1 rs2781666 SNP is significantly associated with an increased susceptibility to DR in T2DM patients.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 11-LB
Author(s):  
SIMON R. HELLER ◽  
ELISE HACHMANN-NIELSEN ◽  
KAJSA KVIST

2020 ◽  
Vol 21 (14) ◽  
pp. 1152-1160
Author(s):  
Imadeldin Elfaki ◽  
Rashid Mir ◽  
Faisel Mohammed Abu-Duhier ◽  
Chandan Kumar Jha ◽  
Adel Ibrahim Ahmad Al-Alawy ◽  
...  

Background:: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represents 20% CYP proteins in liver cells and is a crucial member of CYPs superfamily. CYP2C19 metabolizes very important drugs such as antiulcer drug omeprazole, the antiplatelet drug clopidogrel and anticonvulsant mephenytoin. Single nucleotide polymorphisms (SNPs) of CYP genes have been associated with unexpected drug reactions and diseases in different populations. Objective:: We examined the associations of CYP2C9*3 (rs1057910) and CYP2C19*3 (rs4986893) with T2D in Saudi population. Methods:: We used the allele-specific PCR (AS-PCR) and DNA sequencing in 111 cases and 104 controls for rs1057910, and in 119 cases and 110 controls for rs4986893. Results:: It is indicated that the genotype distribution of rs1057910 in cases and controls were not significantly different (P=0.0001). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and controls was significantly different (P=0.049). The AA genotype of rs4986893 may be associated in increased risk to T2D with OR=17.25 (2.06-143.8), RR=6.14(0.96-39.20), P=0.008. Conclusion:: The CYP2C9*3 (rs1057910) may not be associated with T2D, while CYP2C19*3 (rs4986893) is probably associated with T2D. These findings need to be validated in follow-up studies with larger sample sizes and different populations.


2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


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