CTLA-4 polymorphism 49A–G is associated with placental abruption and preeclampsia in Finnish women

Jääskeläinen, Ester; Toivonen, Sari; Keski‐Nisula, Leea; Paattiniemi, Eeva-Liisa; Helisalmi, Seppo; Punnonen, Kari; Heinonen, Seppo

doi:10.1515/cclm.2008.034

Cited by 22 publications

(19 citation statements)

References 30 publications

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“…Although little is known about the functional role of this polymorphism, other investigators have reported that variations in noncoding regions may influence the mRNA of the ICOS gene and subsequently affect its expression. 29,31 Jääskeläinen et al 18 did not detect an association between the CTLA-4 +49 genotype and PE, but did detect an increased frequency of the G allele in Finnish PE patients. In contrast, an increased frequency of the GA genotype was reported among Iranian women with severe PE.…”

Section: Discussionmentioning

confidence: 91%

“…12 Most association studies between pregnancy and immunoregulatory molecules have focused mainly on CTLA-4. 17,18,27 The T regulatory (Treg) cells that express the activation marker CTLA-4 are critical for the maintenance of maternal tolerance to fetal antigens. 8,9 Additionally, a decreased ratio of CTLA-4(+)/CD28(+) expression, both in peripheral blood and in deciduas, seems to be associated with pregnancy loss.…”

Section: Discussionmentioning

confidence: 99%

“…The first study involved a small group of Iranian patients 17 and suggested that heterozygosis could be a predisposing factor for severe PE. However, Jääskeläinen et al 18 analyzed the same polymorphism in a Finnish population and reported that the G allele appeared to be the risk allele for PE. To the best of our knowledge, there have been no previous studies assessing the association between PE and the CD28 or ICOS genetic polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

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Immunoregulatory gene polymorphisms in women with preeclampsia

et al. 2010

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The costimulatory molecules CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) (cytotoxic T-lymphocyte-associated antigen-4) and inducible costimulator (ICOS) are believed to have a critical modulatory role in the immune response. However, few studies have been performed on the role of these immune regulatory molecules and their polymorphisms in women with preeclampsia (PE). The aim of our study was to evaluate the CTLA4 (+49 A/G) (rs 231775), CD28 (+17 T/C) (rs 3116496) and ICOS (À1564 T/C) (rs 4675378) gene polymorphisms in Brazilian women with PE. This case-control study included 130 patients with PE and 261 control women without any obstetric or systemic disorders. Genomic DNA was extracted from peripheral blood, and the polymorphism genotyping was performed by digesting the PCR products with the restriction endonucleases BbvI (CTLA-4), AfeI (CD28) and AluI (ICOS). Data were analyzed by v 2 or Fisher's exact test; a P-value of o0.05 was considered as significant. There were significant differences in the ICOS genotype and allelic frequencies between the PE and control groups (P¼0.01 and P¼0.01, respectively). We found a significantly lower frequency of the ICOS (À1564) T allele in women with mild PE compared with the controls. There were no differences in the CTLA-4 (+49 A/G) and CD28 (+17 T/C) genotypes and allelic frequencies between the PE patients and controls. Our data suggest that PE is associated with ICOS, but is not associated with the CTLA-4 or CD28 gene polymorphisms.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunoregulatory gene polymorphisms in women with preeclampsia

et al. 2010

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“…It has been hypothesized that peripheral CTLA-4 expression may help maintain maternal-fetal tolerance and protect against immune injury [69][70][71][72]. CTLA-4 expression has been demonstrated in a variety of solid and hematologic malignancies [73][74][75][76].…”

Section: Mechanism Of Ihmentioning

confidence: 99%

Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights

2015

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Hypophysitis occurs in a significant minority of patients treated with Ipi, in contrast to the relative rarity of idiopathic autoimmune hypophysitis or hypophysitis after treatment with other immunotherapies. Recently published cohorts have described the clinical presentation and management of IH and longitudinal outcomes in these patients. Additional studies with Ipi and other emerging agents have helped identify potential risk factors for the development of immunotherapy-related hypophysitis and possible underlying mechanisms for IH. Clarification of the mechanism(s) for IH may enhance our understanding of idiopathic autoimmune hypophysitis and could have potential therapeutic applications.

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“…Increasing evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with systemic oxidative stress and resultant endothelial damage plays a crucial role in the pathogenesis of the disease (2,3). The development of preeclampsia is influenced by both genetic and environmental risk factors, suggesting a multifactorial inheritance (4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Plasma osteopontin concentrations in preeclampsia – is there an association with endothelial injury?

Stenczer

Rigó

Prohászka

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: It has been previously reported that plasma osteopontin (OPN) concentrations are increased in cardiovascular disorders. The goal of the present study was to determine plasma OPN concentrations in healthy pregnant women and preeclamptic patients, and to investigate their relationship to the clinical characteristics of the study subjects and to markers of inflammation wC-reactive protein (CRP)x, endothelial activation wvon Willebrand factor antigen (VWF:Ag)x or endothelial injury (fibronectin), oxidative stress wmalondialdehyde (MDA)x and trophoblast debris (cellfree fetal DNA). Methods: Forty-four patients with preeclampsia and 44 healthy pregnant women matched for age and gestational age were involved in this case-control study. Plasma OPN concentrations were measured with ELISA. Serum CRP concentrations were determined with an autoanalyzer using the manufacturer's reagents. Plasma VWF:Ag was quantified by ELISA, while plasma fibronectin concentrations were measured by nephelometry. Plasma MDA concentrations were estimated by the thiobarbituric acid-based colorimetric assay. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time PCR analysis of the sexdetermining region Y (SRY) gene. For statistical analyses, non-parametric methods were applied.

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CTLA-4 polymorphism 49A–G is associated with placental abruption and preeclampsia in Finnish women

Abstract: Our data suggest that the 49A-G polymorphism in the CTLA-4 gene is associated with the development of placental abruption and preeclampsia, with women having the G allele being at risk.

Cited by 22 publications

References 30 publications

Immunoregulatory gene polymorphisms in women with preeclampsia

Immunoregulatory gene polymorphisms in women with preeclampsia

Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights

Plasma osteopontin concentrations in preeclampsia – is there an association with endothelial injury?

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