Characterization of human Collagen XVIII promoter 2: Interaction of Sp1, Sp3 and YY1 with the regulatory region and a SNP that increases transcription in hepatocytes

Armelin‐Correa, Lucia; Lin, Chin Jia; Barbosa, Angela Silva; Bagatini, Kelly; Winnischofer, Sheila Maria Brochado; Sogayar, Mari Cleide; Passos‐Bueno, Maria Rita

doi:10.1016/j.matbio.2005.08.003

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…However, based on the documented properties of N104ES, it is provocative to speculate that this functional variant impacts on PAH outcomes through the diminished angiostatic activity of the altered peptide. Although multiple studies have examined, with variable results, the association of Col18a1 SNPs with development and severity of solid and liquid tumors (48)(49)(50)(51)(52), our data are the first to formally associate natural variants in Col18a1 to cardiovascular disease, altered serum levels, and PAH mortality.…”

Section: Discussionmentioning

confidence: 94%

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Damico

Kolb

Valera

et al. 2015

Am J Respir Crit Care Med

102

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Rationale: Pulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH.Objectives: We sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH.Methods: We measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minutewalk distance, invasive hemodynamics, and laboratory chemistries.Measurements and Main Results: Serum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality.Conclusions: Our data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.

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Section: Discussionmentioning

confidence: 94%

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Damico

Kolb

Valera

et al. 2015

Am J Respir Crit Care Med

102

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“…We cannot exclude the possibility that the mutated allele is in linkage disequilibrium with another one, which would be actually the responsible for the phenotype. Recently, we verified that allele c.1135T is in linkage disequilibrium with the G allele of the polymorphism -700G>A, which confers higher transcription levels to this collagen [37].…”

Section: Discussionmentioning

confidence: 70%

“…Both probes produced at least four specific complexes (A, B, C and D) (Fig. 3 A, B) and probe -700G the complex X previously described (Armelin-Correa et al, 2005). Oct-1 produced an extra complex just over complex D in both probes (Fig.…”

Section: Functional Analysis Of the Of Snp-700t/g And Oct1 Binding Sitementioning

confidence: 62%

“…Since different C/EBPs family members interact with common recognition sequence, these results strongly suggest that C/EBPα and C/EBPβ are important for COL18A1 transcription in hepatocytes and are responsible for its tissue specific expression. These C/EBP binding sites neighbour Sp1, Sp3 and YY1 sites, characterizing a cluster of transcription factors in COL18A1 promoter 2 (Armelin-Correa et al, 2005). Further experiments will elucidate how the interactions among these factors regulate collagen XVIII in hepatocytes.…”

Section: Discussionmentioning

confidence: 98%

“…Plasmids pGL3-1487T, pGL3-1487G, pGL3-186 were previously constructed by us (Armelin-Correa et al, 2005). pGL3-Basic (Promega, …”

Section: Plasmidsmentioning

confidence: 99%

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Estudo da região promotora do gene do colágeno XVIII humano

Correa¹

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Study of the Association Between Polymorphisms of the COL1A1 Gene and HBV-Related Liver Cirrhosis in Chinese Patients

et al. 2008

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To investigate the association between polymorphisms of the COL1A1 gene and liver cirrhosis. A total of 111 liver cirrhotic patients and 95 matched controls were recruited. Polymorphisms -1997T>G, -1663 ins/del T and -1363C>G of the COL1A1 gene were detected by direct sequencing. The activities of the putative promoters containing these polymorphisms were analyzed by means of the reporter gene system. No polymorphism at -1663 ins/del T was observed in any subject. Linkage disequilibrium was shown between -1997T>G and -1363C>G. The frequency of haplotype -1997T/-1363C was significantly higher in patients than that in controls. The putative promoters containing -1997T/-1363C resulted in higher reporter gene activity in LX-2. Strong transcriptional inhibition by IFN gamma was shown in both cells. The T allele at -1997 of COL1A1 is crucial to the increased transcriptional activity. COL1A1 gene polymorphism might be associated with liver fibrogenesis.

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Characterization of human Collagen XVIII promoter 2: Interaction of Sp1, Sp3 and YY1 with the regulatory region and a SNP that increases transcription in hepatocytes

Cited by 13 publications

References 36 publications

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension

Estudo da região promotora do gene do colágeno XVIII humano

Study of the Association Between Polymorphisms of the COL1A1 Gene and HBV-Related Liver Cirrhosis in Chinese Patients

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