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Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes
Jennifer L Bento, Donald W Bowden, Josyf C Mychaleckyj, Shohei Hirakawa, Stephen S Rich, Barry I Freedman, Fernando Segade
BMC Medical Genetics , 2005, DOI: 10.1186/1471-2350-6-42
Abstract: Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM.Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls.From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans.Multiple genetic studies have been carried out that link human chromosome 20q13.1-13.2 to type 2 diabetes (T2DM) [1-5]. This linkage evidence has led investigators to search for T2DM susceptibility genes in this genomic region. Our laboratory has carried out analysis of specific genes [6-8] and developed high resolution physical maps of the region [9-11]. In an association analysis of genetic markers Price et al. [12] identified three regions of T2DM susceptibility. Among the genes mapped to the linkage disequilibrium regions, a novel facilitative glucose transporter (GLUT) was identified and designated GLUT10 (gene symbol SLC2A10) [6,13]. The gene spans 28 kb of genomic sequence, is split into 5 exons and 4 introns [6,13] and is expressed mainly in heart, liver, lung, skeletal muscle, pancreas, placenta, thyroid, and adipose tissue [6,13
Methylenetetrahydrofolate reductase polymorphism 677C>T is associated with peripheral arterial disease in type 2 diabetes
Rebecca L Pollex, Mary Mamakeesick, Bernard Zinman, Stewart B Harris, Anthony JG Hanley, Robert A Hegele
Cardiovascular Diabetology , 2005, DOI: 10.1186/1475-2840-4-17
Abstract: The 677C>T MTHFR gene polymorphism was genotyped in 138 subjects of Oji-Cree descent. Participants were selected from a community-wide survey that included PAD assessment by ankle-brachial index (ABI) measurement, and also intermittent claudication assessment by the Rose questionnaire.MTHFR 677T allele carriers had an increased risk of PAD with an odds ratio of 3.54 (95% CI 1.01, 12.4), P = 0.049, after adjustment for age, sex, duration of diabetes, hypertension, current smoking habits, and use of insulin or oral treatment for diabetes. None of these additional co-variables was significantly associated with PAD. No association was found between MTHFR genotype and intermittent claudication.The genetic influence of the MTHFR 677C>T genotype on diabetic PAD is modest, yet for the Oji-Cree it is a major risk factor in comparison to other traditional risk factors.Peripheral arterial disease (PAD) of the lower extremities, due to atherosclerosis occurring at the aortic bifurcation, femoral and popliteal arteries, commonly manifests as asymptomatic changes in intermediate phenotypes such as the ankle-brachial index (ABI). The most common symptom experienced is the aches and pains of intermittent claudication, and in extreme situations, individuals may develop gangrene and require lower-limb amputations [1]. While most subjects with PAD remain asymptomatic, all have markedly increased risk of developing cardiovascular disease, as PAD is fundamentally a sign of systemic atherosclerosis. Compared with age-matched controls, patients with intermittent claudication have a threefold increase in cardiovascular mortality [2,3] and a low ABI has been shown to be an independent predictor of both all-cause and cardiovascular mortality [4,5]. The presence of diabetes is associated with a doubling of PAD risk [6]; up to 15% of subjects with type 2 diabetes can have clinically significant PAD [6,7]. Other well-known risk factors for PAD include hypertension, dyslipidemia, and smoking [1]
Haptoglobin genotype predicts development of coronary artery calcification in a prospective cohort of patients with type 1 diabetes
Melissa Simpson, Janet K Snell-Bergeon, Gregory L Kinney, Orit Lache, Rachel Miller-Lotan, Yefim Anbinder, Marian J Rewers, Andrew P Levy
Cardiovascular Diabetology , 2011, DOI: 10.1186/1475-2840-10-99
Abstract: CAC was measured three times in six years among 436 subjects with type 1 diabetes and 526 control subjects participating in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Hp typing was performed on plasma samples by polyacrylamide gel electrophoresis.The Hp 2-2 genotype predicted development of significant CAC only in subjects with diabetes who were free of CAC at baseline (OR: 1.95, 95% CI: 1.07-3.56, p = 0.03), compared to those without the Hp 2-2 genotype, controlling for age, sex, blood pressure and HDL-cholesterol. Hp 2 appeared to have an allele-dose effect on development of CAC. Hp genotype did not predict CAC progression in individuals without diabetes.Hp genotype may aid prediction of accelerated coronary atherosclerosis in subjects with type 1 diabetes.Coronary artery disease (CAD) is the leading cause of death in patients with type 1 diabetes and CAD mortality is 2-4 higher among type 1 diabetes patients than in subjects without diabetes [1,2]. While hyperglycemia and conventional cardiovascular risk factors contribute to this increased risk, they do not account for all of the excess risk. Therefore additional markers are needed to predict which individuals with type 1 diabetes are at greatest risk for developing CAD [3]. Coronary artery calcium (CAC) is a powerful marker of the coronary artery plaque burden [4]. Both the presence and progression of CAC have been shown to predict CAD events [5]and mortality [6].Haptoglobin (Hp) is a protein whose primary function is to modulate the fate and toxicity of extracorpuscular hemoglobin [7]. The Hp protein is polymorphic with two classes of alleles, designated 1 and 2. In most populations of European ancestry, the prevalence of the Hp 1-1 genotype is < 20%; Hp 2-1 and Hp 2-2 have approximately equal frequencies [8]. The protein products of the Hp 1 and Hp 2 alleles are structurally and functionally distinct. The Hp 1 protein mediates more rapid clearance of free hemoglobin and provides super
Increased urine IgM excretion predicts cardiovascular events in patients with type 1 diabetes nephropathy
Rafid Tofik, Ole Torffvit, Bengt Rippe, Omran Bakoush
BMC Medicine , 2009, DOI: 10.1186/1741-7015-7-39
Abstract: This is an observational study of 139 patients with type1 diabetes mellitus (79 males and 60 females) under routine care at the diabetic outpatient clinic at the Lund University Hospital. The median follow-up time was 18 years (1 to 22) years. Urine albumin and urine IgM concentration were measured at time of recruitment.Overall 32 (14 male and 18 female) patients died in a cardiovascular event and 20 (11 male and 9 female) patients reached end-stage renal disease. Univariate analysis indicated that patient survival and renal survival were inversely associated with urine albumin excretion (RR = 2.9 and 5.8, respectively) and urine IgM excretion (RR = 4.6 and 5.7, respectively). Stratified analysis demonstrated that in patients with different degrees of albuminuria, the cardiovascular mortality rate and the incidence of end-stage renal disease was approximately three times higher in patients with increased urine IgM excretion.An increase in urinary IgM excretion in patients with type 1 diabetes is associated with an increased risk for cardiovascular mortality and renal failure, regardless of the degree of albuminuria.Diabetic nephropathy (DN) develops in up to 30% of patients who have had diabetes for more than 20 years [1,2]. DN is characterized by persistent albuminuria, elevated blood pressure, and progressive decline in renal function [3]. Development of DN is associated with an increased risk of cardiovascular (CV) complications and mortality [4,5]. However, a large interindividual variation in the rate of decline in kidney function and mortality has been reported [3,6]. This highlights the need for identification of risk factors and early predictors of progression. An increased urinary albumin excretion is an early sign of DN. Impairment of the tubular protein reabsorption or in the charge-selectivity of the glomerular filtration barrier are probably the major causes of albuminuria in the early stages of type 1 DN [7]. An impairment of the glomerular size-selec
A1C predicts type 2 diabetes and impaired glucose tolerance in a population at risk: the community diabetes prevention project
Silmara AO Leite, Robyn L Anderson, David M Kendall, Arlene M Monk, Richard M Bergenstal
Diabetology & Metabolic Syndrome , 2009, DOI: 10.1186/1758-5996-1-5
Abstract: A total of 388 individuals (22% male, age 46 + 11 years) at risk for T2DM were randomized to Standard (n = 182) or Intervention (n = 206) care and evaluated at baseline and 5 annual follow-up visits, including blood pressure, BMI, A1C, lipids, urine albumin/creatinine ratio, VO2max, fasting glucose, insulin and C-peptide. The Standard group received results of annual lab tests and quarterly newsletters, while the Intervention group received quarterly newsletters and detailed discussions of lab results, routine self-directed activities, semi-annual group meetings and monthly telephone calls for ongoing support.Overall, 359 (93%) returned for at least one follow-up visit and 272 (70%) completed the final 5-year assessment. Return rates, changes in measures and incidence of IGT/T2DM were similar between groups. Low cardiorespiratory fitness (VO2max) was the most prevalent baseline abnormality. A1C and BMI were significant predictors of IGT/T2DM after controlling for other factors. The risk of IGT/T2DM within 5 years was 17.16 (95% CL: 6.169, 47.736) times greater for those with baseline A1C>=5.8% as compared to those <5.8% (p < 0.0001).Baseline A1C>=5.8% was a significant predictor of IGT/T2DM within 5 years in a population at high risk for T2DM. A1C is routinely performed among patients with diabetes, however these data and other evidence suggest that it may also be a useful tool for risk assessment and screening.Diabetes is a chronic disease affecting 171 million of people in the world [1]. The total cost of care for diabetes and its associated complications in 2002 was estimated to be $132 billion [2]. It is estimated that by the time individuals are diagnosed with type 2 diabetes (T2DM), they have had abnormal glucose levels for approximately 10-12 years [3,4]. At the time of diagnosis, as many as 10 to 20% of individuals already has early diabetes complications due to years of undetected hyperglycemia [3,5,6]. Early diagnosis and aggressive treatment aimed at norm
Urinary type IV collagen excretion predicts an increased urinary albumin-to-creatinine ratio in normoalbuminuric patients with diabetes  [PDF]
Susumu Ogawa, Masato Matsushima, Masashi Okamura, Miho Senda, Takuya Sakamoto, Kazuhiro Nako, Sadayoshi Ito
Journal of Diabetes Mellitus (JDM) , 2012, DOI: 10.4236/jdm.2012.24065
Abstract: Aims: We evaluated whether urinary excretion of type IV collagen (U-COL) may predict an increase in the urinary albumin-to-creatinine ratio (ACR) and what factors regulate U-COL in 145 normoalbuminuric patients with type 2 diabetes. Methods: We measured HbA1c, systolic blood pressure (SBP), urinary 8-hydroxydeoxyguanosine (8-OHdG) and monocyte chemoattractant protein (MCP)-1 at start of this study (Baseline), ACR and U-COL in addition to these measurements at one year later (Evaluation-1), and ACR and SBP after two years of the Evaluation-1 (Evaluation-2). The relationships were investigated between the increase of ACR and the U-COL. The effect of angiotensin receptor blockers (ARB) treatment on the correlations between U-COL and ACR at Evaluation-2 on one hand, and between U-COL and percent change of ACR on the other, was also analyzed. Furthermore, we investigated whether the increase in 8-OHdG and in MCP-1 in a year prior to the Evaluation-1 were risk factors of the rise in U-COL levels. Results: Both U-COL and SBP at Evaluation-1, but not ARB treatment, were independent risk factors for an increased ACR after 2 years. ARB treatment significantly suppressed the increase in ACR after 2 years in patients with higher U-COL excretion. The percentage changes in 8-OHdG (%8-OHdG) and MCP-1 (%MCP-1) in one year prior to Evaluation-1 measurements are independent risk factors for U-COL. HbA1c and SBP values one year prior to Evaluation-1 are independent risk factors not only for %8-OHdG but also, for baseline U-COL. The %8-OHdG is an independent risk factor for %MCP-1. Conclusions: U-COL may predict an increase in the ACR. The U-COL seems to be increased with oxidative stress and inflammation induced by past hyperglycemia.
Genetic Associations with Diabetes: Meta-Analyses of 10 Candidate Polymorphisms  [PDF]
Linlin Tang, Lingyan Wang, Qi Liao, Qinwen Wang, Leiting Xu, Shizhong Bu, Yi Huang, Cheng Zhang, Huadan Ye, Xuting Xu, Qiong Liu, Meng Ye, Yifeng Mai, Shiwei Duan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070301
Abstract: Aims The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility. Methods Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes. Results A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01), IL2RA rs11594656 (OR = 0.86, 95% CI = 0.82–0.91, P<0.00001), and CLEC16A rs725613 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01). APOA5 ?1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR = 1.27, 95% CI = 1.03–1.57, P = 0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C. Conclusion Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 ?1131T/C are risky factors of T1D and T2D, respectively.
New representations of Padé and Padé-type approximants  [PDF]
Claude Brezinski,Michela Redivo-Zaglia
Mathematics , 2014,
Abstract: Pad\'e approximants are rational functions whose series expansion match a given series as far as possible. These approximants are usually written under a rational form. In this paper, we will show how to write them also under two different barycentric forms, and under a partial fraction form, depending on free parameters. According to the choice of these parameters, Pad\'e-type approximants can be obtained under a barycentric or a partial fraction form.
Integral representations for Padé-type operators  [PDF]
Nicholas J. Daras
Journal of Applied Mathematics , 2002, DOI: 10.1155/s1110757x02112125
Abstract: The main purpose of this paper is to consider an explicit form of the Padé-type operators. To do so, we consider the representation of Padé-type approximants to the Fourier series of the harmonic functions in the open disk and of the L p-functions on the circle by means of integral formulas, and, then we define the corresponding Padé-type operators. We are also oncerned with the properties of these integral operators and, in this connection, we prove some convergence results.
On the convergence of type I Hermite-Padé approximants  [PDF]
G. López Lagomasino,S. Medina Peralta
Mathematics , 2013,
Abstract: Pad\'e approximation has two natural extensions to vector rational approximation through the so called type I and type II Hermite-Pad\'e approximants. The convergence properties of type II Hermite-Pad\'e approximants have been studied. For such approximants Markov and Stieltjes type theorems are available. To the present, such results have not been obtained for type I approximants. In this paper, we provide Markov and Stieltjes type theorems on the convergence of type I Hermite-Pad\'e approximants for Nikishin systems of functions.
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