Functional Polymorphism in the<i>Suppressor of Cytokine Signaling 1</i>Gene Associated with Adult Asthma

Harada, Michishige; Nakashima, Kazuko; Hirota, Tomomitsu; Shimizu, Makiko; Doi, Satoru; Fujita, Kimie; Shirakawa, Taro; Enomoto, Tadao; Yoshikawa, Mamoru; Moriyama, Hiroshi; Matsumoto, Kenji; Saito, Hirohisa; Suzuki, Yôichi; Nakamura, Yusuke; Tamari, Mayumi

doi:10.1165/rcmb.2006-0090oc

Cited by 94 publications

(85 citation statements)

References 34 publications

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“…For the purpose of this study, we selected this well-defined single nucleotide polymorphism as it has been previously shown to have functional consequences (Harada et al, 2007). Based on the observed prevalence of the minor del allele, our study had 80% power to detect a relative risk of 1.67 with a significance level (alpha) of 0.05 (two-tailed) between CC cases and controls.…”

Section: Discussionmentioning

confidence: 99%

“…The procedure for detecting the SOCS-1 -1478CA>del polymorphism was based on PCR amplification (forward primer: 5'-TGTCGTCCAGCTGCACCTC-3'; reverse primer: 5'-ACCACAGGCTTCAGAGGAAC-3'), restriction cleavage with DdeI (New England Biolabs, Ipswich, MA, USA) and separation of the DNA fragments by 3% agarose gel electrophoresis [figure1], as previously described (Harada et al, 2007). For quality control, genotyping analyses were done blind with respect to case/control status, and a random 25% of the samples were repeated.…”

Section: Genotypingmentioning

confidence: 99%

“…In particular, evidence suggests that SOCS-1 acts as a critical regulator of the IFN-γ (Piganis et al, 2011) and IL-4 (Losman et al, 1999) signaling pathways, which are both involved in the pathogenesis of CC (Landi et al, 2007;Slattery et al, 2011). A functional SOCS-1 promoter polymorphism (-1478CA>del) has been shown to increase SOCS-1 transcription in vitro (Harada et al, 2007). Notably, a high tumor-specific expression of SOCS1 has recently suggested a direct tumor-promoting function of SOCS1 (Zhang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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The SOCS-1 -1478CA/del Polymorphism is not Associated with Colorectal Cancer or Age at Onset in Turkish Subjects

Hartavi

Kurt²,

Oral³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of many cytokine signaling pathways and its abnormal expression has been identified in several human malignancies, suggesting potential roles in carcinogenesis. The aim of this study was to investigate any association between the functional SOCS-1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in a Turkish clinical sample. Materials and Methods: A total of 122 subjects were enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The odds ratio of the del allele for CC relative to the CA allele was not significantly different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did not change after adjustment for age and sex on multivariable regression analysis (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was analyzed among CC patients in relation to the age at disease onset, we found no significant differences between subjects with the del/del, CA/del, and CA/CA genotypes. Conclusions: The results of our study did not point towards a major role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish subjects.

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Section: Discussionmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The SOCS-1 -1478CA/del Polymorphism is not Associated with Colorectal Cancer or Age at Onset in Turkish Subjects

Hartavi

Kurt²,

Oral³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The details of these subjects have been described elsewhere. 10,12,14 For childhood controls and the investigation of total and specific IgE levels, we recruited children attending an elementary school in Chiba City, Japan. The clinical characteristics of this population as well as inclusion and exclusion criteria have been described previously.…”

Section: Study Populationmentioning

confidence: 99%

“…12 The re-evaluation of these associations is conditioned by the limitations of the original reports in which childhood asthma included subjects with nonatopic asthma and those who were o4 years of age. The adult asthma cases also included nonatopic asthma in some of these reports.…”

Section: Introductionmentioning

confidence: 99%

Replication of genetic association studies in asthma and related phenotypes

et al. 2010

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In asthma genetics, the association of highly replicated susceptibility genes lacks consistency across populations. To identify genuine associations, we investigated the reproducibility of the 23 most promising asthma and asthma-related candidate genes in a moderately sized sample from the Japanese population. We compared the frequency of 33 polymorphisms in unrelated cases and controls and tested for their association with asthma, atopy and serum total IgE levels using allele frequency, codominant, dominant and recessive genotype models. On the basis of the consistency of our findings with previous metaanalyses and large replication studies, IL13, TNF, ADAM33, IL4RA and TBXA2R might represent common major asthma and asthma-related trait genes. Individual gene assessment was extended to the interactions between two polymorphisms using our original method. Interactions between TBXA2R and ADAM33, and IL4RA and C3 were suggested to increase the risk for childhood and all asthma (adult and childhood asthma combined). The confirmation of previously reported associations between gene polymorphisms and phenotypes was problematic when as few as several hundred samples per group were used. Stratification of the subjects by environmental factors or other confounding factors may be necessary to improve the sensitivity and reliability of association results. Keywords: association; asthma; atopy; polymorphism; replication INTRODUCTIONAsthma is a heritable trait 1 and investigations to determine the genetic components underlying asthma using linkage mapping and the candidate gene approach have been carried out. By 2006, more than 100 genes were associated with asthma and asthma-related phenotypes; 2 25 of these genes have been replicated in more than six independent association studies. In 2008, this list was complemented with an additional three genes, FLG, NAT2 and CCL15. 3 However, no single polymorphic marker or gene locus has been unanimously labeled as a strong and independent genetic determinant of asthma, and the results for the highly replicated genes have been inconsistent across the tested populations. 3 To identify true associations, it is of critical importance to comprehensively replicate the initial finding. 4 To this aim, we investigated whether the 23 most replicated genes for asthma and asthma-related phenotypes were positively associated with extrinsic childhood and adult asthma, atopy and total serum IgE levels in a moderately sized sample drawn from the Japanese population.We also tested eight genes that were significantly associated with asthma in our subjects: IL13, 5 TBXA2R, 6 GSTP1, 7 ADAM33, 8 MMP9, 9 IL12B, 10 C3 11 and SOCS1. 12 The re-evaluation of these associations is

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Role of Transcription Factors in Pulmonary Artery Smooth Muscle Cells: An Important Link to Hypoxic Pulmonary Hypertension

Mise

Wang

Zheng

2017

Advances in Experimental Medicine and Biology

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Hypoxia, namely a lack of oxygen in the blood, induces pulmonary vasoconstriction and vasoremodeling, which serve as essential pathologic factors leading to pulmonary hypertension (PH). The underlying molecular mechanisms are uncertain; however, pulmonary artery smooth muscle cells (PASMCs) play an essential role in hypoxia-induced pulmonary vasoconstriction, vasoremodeling, and PH. Hypoxia causes oxidative damage to DNAs, proteins, and lipids. This damage (oxidative stress) modulates the activity of ion channels and elevates the intracellular calcium concentration ([Ca], Ca signaling) of PASMCs. The oxidative stress and increased Ca signaling mutually interact with each other, and synergistically results in a variety of cellular responses. These responses include functional and structural abnormalities of mitochondria, sarcoplasmic reticulum, and nucleus; cell contraction, proliferation, migration, and apoptosis, as well as generation of vasoactive substances, inflammatory molecules, and growth factors that mediate the development of PH. A number of studies reveal that various transcription factors (TFs) play important roles in hypoxia-induced oxidative stress, disrupted PAMSC Ca signaling and the development and progress of PH. It is believed that in the pathogenesis of PH, hypoxia facilitates these roles by mediating the expression of multiple genes. Therefore, the identification of specific genes and their transcription factors implicated in PH is necessary for the complete understanding of the underlying molecular mechanisms. Moreover, this identification may aid in the development of novel and effective therapeutic strategies for PH.

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Functional Polymorphism in theSuppressor of Cytokine Signaling 1Gene Associated with Adult Asthma

Cited by 94 publications

References 34 publications

The SOCS-1 -1478CA/del Polymorphism is not Associated with Colorectal Cancer or Age at Onset in Turkish Subjects

The SOCS-1 -1478CA/del Polymorphism is not Associated with Colorectal Cancer or Age at Onset in Turkish Subjects

Replication of genetic association studies in asthma and related phenotypes

Role of Transcription Factors in Pulmonary Artery Smooth Muscle Cells: An Important Link to Hypoxic Pulmonary Hypertension

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