Association of alleles at polymorphic sites in the osteopontin encoding gene in young type 1 diabetic patients

Marciano, Renato; d’Annunzio, Giuseppe; Minuto, Nicola; Pasquali, Lorenzo; Santamaria, Giuseppe; Duca, Marco Di; Ravazzolo, Roberto; Lorini, Renata

doi:10.1016/j.clim.2008.11.004

Cited by 26 publications

(24 citation statements)

References 42 publications

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“…Together, we assume that OPN transcription in patients with À156G allele is more susceptible to Runx2-dependent upregulation and that patients carrying À156G allele demonstrated impaired diastolic function compared with À156del/À156del patients. In a previous report, one of three functional polymorphisms on OPN promoter (À66T/G) is associated with the onset of Type 1 diabetes in young female patients, 37 suggesting OPN transcription might be related with pathogenesis of type1 DM. As our study includes Type 2 DM patients, but not Type 1, it is reasonable that no statistical association exists between the frequency of À156del/G and incidence of DM in our subjects, though further investigation might be needed to assess the association of OPN promoter genotypes with the onset and the progression of Type 2 diabetes.…”

Section: Renin-angiotensin System and Opn Expressionmentioning

confidence: 92%

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

et al. 2011

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Heart failure with preserved ejection fraction is recently highlighted as a major health problem, and diastolic dysfunction associated with hypertension has a dominant role in the development of heart failure with preserved ejection fraction. Osteopontin (OPN) is a secreted phosphoprotein, which mediates fibrosis. In animal models, OPN is upregulated in response to pressure overload and is thought to be involved in systolic dysfunction. However, the functional role of OPN in diastolic dysfunction is unknown. The guanine base insertion polymorphism at À156 position of the OPN promoter is postulated to upregulate the transcription of OPN in human. To investigate whether À156del/G polymorphism of OPN promoter is associated with diastolic dysfunction in hypertensive hearts, the patients with hypertension have been genotyped for variants of À156del/G polymorphism by genomic sequencing. Diastolic function of the left ventricle was estimated as the ratio of early to atrial filling (E/A ratio), obtained by pulsed-Doppler derived transmitral flow in echocardiographic analysis. The patients with À156G allele displayed lower E/A ratio compared with those with À156del/del genotype, suggesting exacerbated diastolic function. Notably, in case of the population with diabetes mellitus, the patients with À156G allele showed significant association with lower E/A ratio, compared with À156del/À156del patients. Multiple linear regression analysis revealed that prevalence of À156G allele was an independent factor for lowering E/A ratio. The À156del/G genetic variants of OPN promoter were associated with decreased E/A ratio in hypertensive patients. These results suggest that OPN has a functional role in the development of diastolic dysfunction in hypertensive hearts.

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Section: Renin-angiotensin System and Opn Expressionmentioning

confidence: 92%

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

et al. 2011

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“…The SNP tested in SPP1 (rs28357094) has been previously shown to be associated with carotid intima thickness and type 1 diabetes. 19,20 In USMG5, we studied a validated missense polymorphism (serine to proline) (rs11557060).…”

Section: Cinrg Cohortmentioning

confidence: 99%

SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy

Pegoraro¹,

Hoffman

Piva³

et al. 2011

Neurology

198

235

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Objective: Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder.Substantial patient-patient variability in disease onset and progression and response to glucocorticoids is seen, suggesting genetic or environmental modifiers.Methods: Two DMD cohorts were used as test and validation groups to define genetic modifiers: a Padova longitudinal cohort (n ϭ 106) and the Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history cohort (n ϭ 156). Single nucleotide polymorphisms to be genotyped were selected from mRNA profiling in patients with severe vs mild DMD, and genome-wide association studies in metabolism and polymorphisms influencing muscle phenotypes in normal volunteers were studied.

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“…Interestingly, OPN was shown to influence the acute pancreatic islets' response to experimentally induced diabetes in non-obese diabetic (NOD) mice, and genetic studies of single nucleotide polymorphisms (SNPs) in humans suggest that the OPN encoding gene might be associated with an increased susceptibility to the development of type 1 diabetes mellitus (T1DM) (24,25). Moreover, serum OPN levels were demonstrated to strongly predict incipient diabetic nephropathy (DN), cardiovascular events and all-cause mortality in patients with T1DM (26) and were associated with renal failure and left ventricular hypertrophy in patients affected by systemic hypertension (27,28).…”

Section: Introductionmentioning

confidence: 99%

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile

Barchetta¹,

Alessandri

Bertoccini³

et al. 2016

European Journal of Endocrinology

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Objective: Osteopontin (OPN) is a sialoprotein implicated in different immunity and metabolic pathways. Capable of activating dendritic cells and inducing Th1-Th17-mediated tissue damage, OPN plays a significant role in the development/progression of several autoimmune diseases; interestingly, it was also shown that OPN participates in the acute pancreatic islets response to experimentally induced diabetes in non-obese diabetic (NOD) mice. Furthermore, OPN promotes adipose tissue dysfunction, systemic inflammation and insulin resistance. Our aims of this study were to evaluate circulating OPN levels in adult patients with type 1 diabetes mellitus (T1DM) compared to non-diabetic control participants and to unravel clinical and biochemical correlates of OPN concentration. Design: Case-control study. Methods: We enrolled 54 consecutive T1DM patients referred to our diabetes outpatient clinic at Sapienza University of Rome and 52 healthy sex and age-comparable controls. The study population underwent clinical evaluation, blood sampling for biochemistry and complete screening for diabetes complications. Serum OPN levels were measured by MILLIPLEX Multiplex Assays Luminex. Results: T1DM patients had significantly higher serum OPN levels than controls (17.2G12.9 vs 10.5G11.6 mg/ml, PZ0.009). OPN levels correlated with T1DM, higher blood pressure, BMI, creatinine, g-GT, ALP and lower HDL; the association between high OPN levels and T1DM was independent from all confounders. No correlation was shown between OPN and HbA1c, C-peptide, insulin requirement, co-medications and diabetes duration. Conclusions: This study demonstrates for the first time in a case-control study that adults with T1DM have increased serum OPN levels, and that higher OPN concentrations are associated with an unfavorable metabolic profile in these patients.

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Association of alleles at polymorphic sites in the osteopontin encoding gene in young type 1 diabetic patients

Cited by 26 publications

References 42 publications

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile

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