Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India

2021 ◽  
pp. 1-9
Author(s):  
Sartaj Hussain ◽  
Suraj Singh Yadav ◽  
Monisha Banerjee ◽  
Kauser Usman ◽  
Sanjay Khattri

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer,and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated <i>FOXO3</i> gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (<i>p</i> = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69–1.26, <i>p</i> &#x3e; 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (<i>p</i> &#x3c; 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in <i>FOXO3</i> (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 419 ◽  
Author(s):  
Anh-Tuan Tran ◽  
Jeannette Kluess ◽  
Andreas Berk ◽  
Marleen Paulick ◽  
Jana Frahm ◽  
...  

We investigated the effects of feeding sodium sulfite (SoS) treated uncontaminated and Fusarium contaminated maize in a porcine lipopolysaccharide (LPS) challenge model. Eighty piglets (7.59 ± 0.92 kg body weight [BW]) were equally assigned to one of four experimental diets containing 10% maize, either uncontaminated and untreated (CON−, 0.09 mg deoxynivalenol [DON]/kg diet) or uncontaminated and SoS-treated (CON+, wet-preserved with 5 g SoS/kg maize; 0.05 mg DON/kg diet), or prepared with 10% of a Fusarium contaminated maize containing mainly deoxynivalenol (DON), either contaminated and untreated (FUS−, 5.36 mg DON/kg diet), or contaminated and SoS-treated (FUS+, wet-preserved with 5 g SoS/kg maize; 0.83 mg DON/kg diet). At day 42 of experiment, ten pigs of each group were injected intraperitoneally with either 7.5 µg LPS/kg BW or placebo (0.9% NaCl). At 120 min after injection, blood samples were collected to analyse TNF-α, hematological profile, clinical biochemistry as well as the redox status. A significant increase in body temperature and cytokine TNF-α concentration was observed in the LPS-injected piglets. Results for hematology, clinical chemistry and redox status indicate no effects of SoS treatment, with exception of neutrophil counts being significantly more pronounced after feeding the SoS treated FUS maize. In conclusion, SoS treatment of maize did not modulate the LPS-induced acute inflammation.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mani Mokou ◽  
Shan Yang ◽  
Bin Zhan ◽  
Shan Geng ◽  
Kejia Li ◽  
...  

Background. Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods. The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results. Serum Fetuin-B and TNF-α levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-α, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion. Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.


2016 ◽  
Vol 44 (2) ◽  
pp. 638-644 ◽  
Author(s):  
Francis Sanders ◽  
Ben McNally ◽  
Julian L. Griffin

Although the measurement of triacylglycerols (TAGs) by clinical chemistry has been used in the diagnosis of a range of metabolic diseases, such approaches ignore the different species of TAGs that contribute to the total concentration. With the advent of LC and direct infusion forms of MS it is now possible to profile the individual TAGs in blood plasma or tissue extracts. This mini review surveys the information that is obtainable from the lipidomic profiling of TAGs in following metabolic diseases such as type 2 diabetes (T2DM), cardiovascular disease (CVD) and non-alcoholic fatty liver disease, as well as the development of insulin resistance and obesity.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tae Ik Chang ◽  
Haeyong Park ◽  
Dong Wook Kim ◽  
Eun Kyung Jeon ◽  
Connie M. Rhee ◽  
...  

Abstract Polypharmacy is a growing and major public health issue, particularly in the geriatric population. This study aimed to examine the association between polypharmacy and the risk of hospitalization and mortality. We included 3,007,620 elderly individuals aged ≥ 65 years who had at least one routinely-prescribed medication but had no prior hospitalization within a year. The primary exposures of interest were number of daily prescribed medications (1–2, 3–4, 5–6, 7–8, 9–10, and ≥ 11) and presence of polypharmacy (≥ 5 prescription drugs per day). The corresponding comparators were the lowest number of medications (1–2) and absence of polypharmacy. The study outcomes were hospitalization and all-cause death. The median age of participants was 72 years and 39.5% were men. Approximately, 46.6% of participants experienced polypharmacy. Over a median follow-up of 5.0 years, 2,028,062 (67.4%) hospitalizations and 459,076 (15.3%) all-cause deaths were observed. An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18–1.19) and 1.25 (1.24–1.25) in the overall and 1.16 (1.16–1.17) and 1.25 (1.24–1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Vitalina Bashynska ◽  
Alexander Koliada ◽  
Kateryna Murlanova ◽  
Oksana Zahorodnia ◽  
Yuliia Borysovych ◽  
...  

Tobacco smoking is known to be a strong risk factor for developing many diseases. The development and severity of smoking dependence results from interaction of environmental and lifestyle factors, psycho-emotional predispositions, and also from genetic susceptibility. In present study, we investigated polymorphic variants in genes contributed to nicotine dependence, as well as to increased impulsivity, known to be an important risk factor for substance use disorders, in Ukraine population. The genotype frequencies at CYP2A6, DNMT3B, DRD2, HTR2A, COMT, BDNF, GABRA2, CHRNA5, and DAT1 polymorphisms were determined in 171 Ukraine residents, and these data were compared with data for several other European populations and main ethnic groups. It has been found that genotype frequencies for all studied loci are in Hardy-Weinberg equilibrium in the Ukrainian population and correspond to the respective frequencies in European populations. These findings suggest a similar impact of these loci on nicotine dependence in Ukraine. Further studies with larger sample sizes are, however, needed to draw firm conclusions about the effect size of these polymorphisms.


2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Grazyna Deja ◽  
Przemyslawa Jarosz-Chobot ◽  
Joanna Polanska ◽  
Urszula Siekiera ◽  
Ewa Malecka-Tendera

The aim of the study was to assess chosen factors of genetic susceptibility to DMT1: DRB1, DQB1, and TNF-αpolymorphisms-308 (G/A) in children with DMT1 and their up-to-now healthy siblings. Then we tested whether the association between TNF-αgenes and DMT1 is independent of HLA. 87 diabetic children, their 78 siblings, and 85 persons from healthy control group were followed up. The highest risk of DMT1 was connected with alleles: DRB1*0401 (OR = 3.39; CI: 1.55–7.41), DRB1*0301 (OR = 2.72; CI: 1.48–5.01), DQB1*0201 (OR = 4.04; CI: 2.17–7.52), DQB1*0302 (OR = 5.08; CI: 2.54–10.14), and TNF-α-308 A allele (OR = 2.59; CI: 1.23–5.44). Moreover linkage disequilibrium for TNF-α-308 A allele with DRB1*0301 and DQB1*0201 was observed in both diabetic children and their siblings. Diabetic children and their siblings present similar genetic risk factors for DMT1. The association between TNF-α-308 A allele and DMT1 is dependent of HLA-DRB1 and DQB1 alleles.


2005 ◽  
Vol 21 (3) ◽  
pp. 157-165 ◽  
Author(s):  
Carola Seifart ◽  
Alexandra Plagens ◽  
Astrid Dempfle ◽  
Ursula Clostermann ◽  
Claus Vogelmeier ◽  
...  

Apart from cigarette smoking, genetic factors seem to be of importance in the development of lung cancer. The present case-control study investigated frequencies of five inflammatory response gene polymorphisms (TNF-α-308, TNF-β-Intron1-252, IL-6-174, IL-10-819 and IL-10-1082) in patients with lung cancer and controls. The study population consisted of 117 patients with lung cancer (77 patients with NSCLC, including 40 Squamous Cell Carcinoma and 26 Adenocarcinoma, and 40 patients with SCLC), 117 matched controls without pulmonary disease and 243 healthy individuals (population control). Genotype analyses revealed no difference in genotype frequencies using matched-pair analysis. However, in comparison to the population control, the IL-10-1082 genotypes carrying the G allele appeared with higher frequency in the SCLC group (p= 0.006) [SCLC: 84.6%, population controls: 64.6%]. This yields an odds ratio of 3.01 for SCLC (95% CI = [1.21, 7.48]). No associations were seen for all other polymorphisms analysed. The study raises the possibility of a correlation between the IL-10-1082_G allele and the presence of SCLC in a German population. The functional IL-10-1082 polymorphism correlates with altered IL-10 levels and might influence lung cancer susceptibility by altered inflammatory responses in the airways.


QJM ◽  
2017 ◽  
Vol 110 (9) ◽  
pp. 551-557 ◽  
Author(s):  
G. Georgiopoulos ◽  
C. Chrysohoou ◽  
A. Errigo ◽  
G. Pes ◽  
V. Metaxa ◽  
...  

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