Association of functional genetic variants of CTLA4 with reduced serum CTLA4 protein levels and increased risk of idiopathic recurrent miscarriages

Misra, Maneesh Kumar; Mishra, Aditi; Phadke, Shubha R.; Agrawal, Suraksha

doi:10.1016/j.fertnstert.2016.06.011

Cited by 21 publications

(15 citation statements)

References 48 publications

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“…To better understand the combined results of this meta-analysis, some points should be considered. First, investigated polymorphisms of CTLA-4 , MBL , IL-4 and IL-6 were all shown to be correlated with altered transcription activity or protein structure by past basic researches 21–23. So these variations may influence the biological function of CTLA-4/MBL/IL-4/IL-6 , result in immune dysfunction, cause chronic inflammatory or infectious injuries of the stomach and ultimately confer susceptibility to GC.…”

Section: Discussionmentioning

confidence: 99%

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

et al. 2019

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AimsAssociations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε−1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies.MethodsEligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies.ResultsForty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms.ConclusionCollectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.

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Section: Discussionmentioning

confidence: 99%

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

et al. 2019

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“…No significant difference was detected in the frequency of the SNPs of CTLA4 and PDL1, although recent reports have shown associations between the SNPs of CTLA4 (rs231775) and with RPL. [9][10][11] The max-statistic was carried out in order to detect the heredity model of four SNPs of CTLA4, whereas previous studies used only the allelic model to examine the frequency of the SNPs. The current results revealed no significant difference among the four models (dominant, codominant, recessive, log-additive).…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that maternal Treg cells suppress an aggressive allogeneic response that is directed against the fetus and that the early human decidua contains an abundance of CD4 + CD25 bright T cells, which show high expression levels of cytotoxic T lymphocyte‐associated antigen 4 (CTLA4) . Several studies have reported an association between the SNPs of CTLA4 and RPL . According to one study, a decreased number of Treg cells was present in cases of pre‐eclampsia, which appeared to break the maternal tolerance to the fetus …”

Section: Introductionmentioning

confidence: 99%

“…7,8 Several studies have reported an association between the SNPs of CTLA4 and RPL. [9][10][11] According to one study, a decreased number of Treg cells was present in cases of pre-eclampsia, which appeared to break the maternal tolerance to the fetus. 12 However, programmed cell death ligand 1 (PDL1) has been identified as a new member of the B7 family 13 and is a ligand for programmed cell death 1 (PD1), which is expressed on activated T and B cells.…”

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confidence: 99%

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Association of genetic variants of PD1 with recurrent pregnancy loss

Hayashi

Nishiyama

Nakatochi

et al. 2018

Reprod Medicine & Biology

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PurposeProgrammed cell death 1 (PD1) and PD ligand 1 (PDL1) are speculated to have an important role in maintaining a normal pregnancy and there are also a few reports of an association between the single‐nucleotide polymorphisms (SNPs) of PD1 or PDL1 and diseases in humans. The association was examined between the polymorphisms of PD1,PDL1,CTLA4 and recurrent pregnancy loss (RPL).MethodsThe study group consisted of 243 women with two or more pregnancy losses and 176 parous women. The frequency of three SNPs of PD1, two of PDL1, and four of CTLA4 were compared between the patients and controls. Next, the subsequent live birth rates in the patients with RPL with and without risk alleles were examined.ResultsTwo SNPs (rs36084323 and rs3481962) of PD1 were found to occur at significantly higher frequencies in the patient group than in the control group. The subsequent live birth rate of the patients with vs. without the risk alleles of rs36084323 and rs3481962 were 83.3% vs. 83.3% and 81.6% vs. 84.0%, respectively.ConclusionVariations of the PD1 gene were identified as risk factors for RPL. However, the presence or absence of the PD1 risk alleles had no predictive effect on the subsequent pregnancy outcome.

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“…Besides, rs4553808 G allele and rs5742909 T allele were significantly associated with 0.570-fold reduced RSA susceptibility respectively. But Misra et al [ 18 ] suggested that rs4553808 and rs5742909 SNP had no significant association with idiopathic recurrent miscarriages (IRM). This difference might be caused by different ethnicity, region, or sample size.…”

Section: Discussionmentioning

confidence: 99%

Correlation between CTLA4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion

Liu

Qin

et al. 2018

Medicine

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Present study was aimed to detect the influence of cytotoxic T-lymphocyte associated protein 4 (CTLA4) gene polymorphisms for the risk of recurrent spontaneous abortion (RSA), as well as the serum level of CTLA4 protein in RSA patients.One hundred thirty-three RSA patients and 146 healthy persons were recruited in this case–control study. PCR-RFLP was used to genotype the CTLA4 gene polymorphisms both in case and control groups. Serum level of CTLA4 was detected by ELISA kit. Quantitative variables were compared by t test or Mann–Whitney U test between groups. Qualitative variables were evaluated by χ2 test or Fisher exact test. Association strength was expressed by odds ratios (ORs) and 95% confidence intervals (95% CIs).G allele of rs4553808 (P = .027, OR = 0.570, 95% CI = 0.345–0.942) and T allele of rs5742909 (P = .027, OR = 0.570, 95% CI = 0.345–0.942) were distinctly associated with reduced susceptibility of RSA. Distinctly negative association has been discovered between rs231775 AA genotype and RSA susceptibility (P = .040, OR = 0.427, 95% CI = 0.188–0.973). CTLA4 protein had significantly higher serum level in RSA patients than in healthy controls (P = .028). In RSA patients, AA genotype carriers had higher CTLA4 serum level than that GG genotype carriers (17.83 ± 6.35 ng/mL vs 10.41 ± 7.28 ng/mL, P = .039).Minor alleles of CTLA4 polymorphisms might inhibit the RSA susceptibility via upregulated the protein expression level.

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Association of functional genetic variants of CTLA4 with reduced serum CTLA4 protein levels and increased risk of idiopathic recurrent miscarriages

Cited by 21 publications

References 48 publications

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

Association of genetic variants of PD1 with recurrent pregnancy loss

Correlation between CTLA4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion

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