SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C

Naito, Masashi; Matsui, Atsushi; Inao, Mie; Nagoshi, Sumiko; Nagano, Makoto; Ito, Nobuyoshi; Egashira, Tohru; Hashimoto, Michie; Mishiro, Shunji; Mochida, Satoshi; Fujiwara, Kenji

doi:10.1007/s00535-005-1558-3

Cited by 64 publications

(55 citation statements)

References 28 publications

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“…Nevertheless, this information provides additional support for a relationship between host genetics and HCV viral clearance and is consistent with several recent reports that evaluated gene expression and gene polymorphisms in individuals with and without sustained virological response to interferon-based regimens (49)(50)(51)(52)(53)(54). Using microarrays in hepatic tissue, Chen and colleagues identified a number of interferon-sensitive genes that correlated with response to antiviral therapy (50).…”

Section: Discussionsupporting

confidence: 81%

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

et al. 2006

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Section: Discussionsupporting

confidence: 81%

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

et al. 2006

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“…Blom further states that many closely linked polymorphic genes derived from the 129 strain and linked to the OPN locus could influence the inflammatory response or resistance to pathogens, including the chemokines Cxcl-1, Cxcl-2, Cxcl-5, Cxcl-9, Cxcl-10, Cxcl-15, and the neuronal nitric oxide synthase, Nos1 (9). Several studies have addressed the effect of allelic polymorphism of OPN in the development of autoimmunity and host defense with varying outcomes (32)(33)(34)(35)(36)(37)(38)(39). Importantly, the C57BL/6 mice used in our study and the C57BL/6 ϫ 129SV mice used in previous studies express the same OPN allele, namely Eta-1 a , which excludes this additional factor from the interpretation (40,41).…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Is Not Required for the Development of Th1 Responses and Viral Immunity

Abel

Freigang²,

Bachmann³

et al. 2005

The Journal of Immunology

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Osteopontin (OPN) has been defined as a key cytokine promoting the release of IL-12 and hence inducing the development of protective cell-mediated immunity to viruses and intracellular pathogens. To further characterize the role of OPN in antiviral immunity, OPN-deficient (OPN−/−) mice were analyzed after infection with influenza virus and vaccinia virus. Surprisingly, we found that viral clearance, lung inflammation, and recruitment of effector T cells to the lung were unaffected in OPN−/− mice after influenza infection. Furthermore, effector status of T cells was normal as demonstrated by normal IFN-γ production and CTL lytic activity. Moreover, activation and Th1 differentiation of naive TCR transgenic CD4+ T cells by dendritic cells and cognate Ag was normal in the absence of OPN in vitro. Contrary to a previous report, we found that OPN−/− mice mounted a normal immune response to Listeria monocytogenes. In conclusion, OPN is dispensable for antiviral immune responses against influenza virus and vaccinia virus.

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“…17,18 Recently, three functional polymorphisms (À66T/G, À156del/G and À443T/C) on the promoter region of OPN gene have been found to affect gene expression by altering transcriptional activity 19 and reported to be associated with several diseases, including pseudoxanthoma elasticum, stroke and chronic hepatitis C. [20][21][22] The insertion of guanine base at position À156 (À156G allele) on the OPN promoter generates a Runx2 binding site so that the binding of Runx2 factor to the À156G position promotes OPN transcription. 19 In the present study, we investigated the association between diastolic dysfunction and the À156del/G polymorphism on the OPN promoter in patients with hypertension.…”

Section: Introductionmentioning

confidence: 99%

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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SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C

Abstract: SNPs in the promoter region of OPN may be useful as a marker to predict the efficacy of IFN-based therapies in patients with chronic hepatitis C, and further investigation regarding their real significance is warranted in a large series of patients.

Cited by 64 publications

References 28 publications

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Osteopontin Is Not Required for the Development of Th1 Responses and Viral Immunity

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

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