The impact of HLA-G 3′ UTR variants and sHLA-G on risk and clinical correlates of schizophrenia

Rajasekaran, Ashwini; Shivakumar, Venkataram; Kalmady, Sunil V.; Narayanaswamy, Janardhanan C.; Subbana, Manjula; Venugopal, Deepthi; Amaresha, Anekal C.; Venkatasubramanian, Ganesan; Berk, Michael; Debnath, Monojit

doi:10.1016/j.humimm.2016.08.013

Cited by 15 publications

(9 citation statements)

References 51 publications

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“…Also, the 14-bp Ins/Del had high LD with +3142 and +3010 SNPs. The variations found in cis were related to their effect when inherited together, as previously described for HLA-G [44–49]. Thus, the composition possibly associated with the risk of kidney allograft rejection by the decrease of HLA-G expression would be +3010 C , +3142 G and 14-bp Ins , whereas +3010 G with +3142 C , and +3142 C with 14-bp Del would be associated with an increase.…”

Section: Discussionsupporting

confidence: 55%

“…The analyses were not able to detect a direct relation regarding the +3010 CC and rejection, but twice as many patients who developed episodes of rejection have this genotype compared to the frequencies of +3010 GG patients, which was associated as a protection factor. The association of +3142 with 14-bp Ins/Del has been the subject of many studies aiming to identify risk factors [45,46,49,51]. However, we suggest that +3010 is a marker to predict the simultaneous presence of +3142 G with 14-bp Ins .…”

Section: Discussionmentioning

confidence: 64%

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The association of HLA-G polymorphisms and the synergistic effect of sMICA and sHLA-G with chronic kidney disease and allograft acceptance

et al. 2019

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The HLA-G and MICA genes are stimulated under inflammatory conditions and code for soluble (sMICA and sHLA-G) or membrane-bound molecules that exhibit immunomodulatory properties. It is still unclear whether they would have a synergistic or antagonistic effect on the immunomodulation of the inflammatory response, such as in chronic kidney disease (CKD), contributing to a better prognosis after the kidney transplantation. In this study, we went from genetic to plasma analysis, first evaluating the polymorphism of MICA , NKG2D and HLA-G in a cohort from Southern Brazil, subdivided in a control group of individuals (n = 75), patients with CKD (n = 94), and kidney-transplant (KT) patients (n = 64). MICA , NKG2D and HLA-G genotyping was performed by polymerase chain reaction with specific oligonucleotide probes, Taqman and Sanger sequencing, respectively. Levels of soluble forms of MICA and HLA-G were measured in plasma with ELISA. Case-control analysis showed that the individuals with haplotype HLA-G*01 : 01/ UTR-4 have a lower susceptibility to develop chronic kidney disease (OR = 0.480; p = 0.032). Concerning the group of kidney-transplant patients, the HLA-G genotypes +3010 GC ( rs1710 ) and +3142 GC ( rs1063320 ) were associated with higher risk for allograft rejection (OR = 5.357; p = 0.013 and OR = 5.357, p = 0.013, respectively). Nevertheless, the genotype +3010 GG (OR = 0.136; p = 0.041) was associated with kidney allograft acceptance, suggesting that it is a protection factor for rejection. In addition, the phenotypic analysis revealed higher levels of sHLA-G ( p = 0.003) and sMICA ( p < 0.001) in plasma were associated with the development of CKD. For patients who were already under chronic pathological stress and underwent a kidney transplant, a high sMICA ( p = 0.001) in pre-transplant proved to favor immunomodulation and allograft acceptance. Even so, the association of genetic factors with differential levels of soluble molecules were not evidenced, we displayed a synergistic effect of sMICA and sHLA-G in response to inflammation. This increase was observed in CKD patients, that when undergo transplantation, had this previous amount of immunoregulatory molecules as a positive factor for the allograft acceptance.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 64%

The association of HLA-G polymorphisms and the synergistic effect of sMICA and sHLA-G with chronic kidney disease and allograft acceptance

et al. 2019

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“…Schizophrenia carrying glutathione S-transferase (GST) A1 * B allele had more severe AHs than non-B carriers (Spalletta et al, 2012). Rajasekaran et al (2016) found an association between (human leukocyte antigen-G) HLA-G 14-bp Ins/Ins genotype and lifetime presence of third person AHs, and this association was more significant in males with schizophrenia. The genotype frequency of matrix metalloproteinase 1 (MMP1) single-nucleotide polymorphism (SNP) rs470558 was reported to be associated with AHs, and its A allele frequency was higher in schizophrenia with AHs (SZ-AH) than schizophrenia without AHs (SZ-non-AH) (Kim et al, 2012).…”

Section: Genetic Research Genetic Factormentioning

confidence: 99%

The Etiology of Auditory Hallucinations in Schizophrenia: From Multidimensional Levels

Shao

Liao

et al. 2021

Front. Neurosci.

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Enormous efforts have been made to unveil the etiology of auditory hallucinations (AHs), and multiple genetic and neural factors have already been shown to have their own roles. Previous studies have shown that AHs in schizophrenia vary from those in other disorders, suggesting that they have unique features and possibly distinguishable mechanisms worthy of further investigation. In this review, we intend to offer a comprehensive summary of current findings related to AHs in schizophrenia from aspects of genetics and transcriptome, neurophysiology (neurometabolic and electroencephalogram studies), and neuroimaging (structural and functional magnetic resonance imaging studies and transcriptome–neuroimaging association study). Main findings include gene polymorphisms, glutamate level change, electroencephalographic alterations, and abnormalities of white matter fasciculi, cortical structure, and cerebral activities, especially in multiple regions, including auditory and language networks. More solid and comparable research is needed to replicate and integrate ongoing findings from multidimensional levels.

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“…Moreover, many types of cancer exhibit an aberrant miR expression profile 27,28 , which modulates the tumor microenvironment via non-cell-autonomous mechanisms 28 and is involved in tumor initiation, progression, metastasis formation and therapy resistance 29 . We here propose that, in analogy with other clinical disorders 30,31 , variable HLA-G 3′UTR sites in combination with the cellular microenvironment may be critical in influencing HLA-G expression.…”

Section: Introductionmentioning

confidence: 96%

HLA-G 3′ untranslated region variants +3187G/G, +3196G/G and +3035T define diametrical clinical status and disease outcome in epithelial ovarian cancer

Schwich

Rebmann

Michita

et al. 2019

Sci Rep

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Expression of the non-classical human leukocyte antigen-G (HLA-G) promotes cancer progression in various malignancies including epithelial ovarian cancer (EOC). As single nucleotide polymorphisms (SNPs) in the HLA-G 3′ untranslated region (UTR) regulate HLA-G expression, we investigated HLA-G 3′UTR haplotypes arranged by SNPs in healthy controls (n = 75) and primary EOC patients (n = 79) and determined soluble HLA-G (sHLA-G) levels. Results were related to the clinical status and outcome. Although haplotype frequencies were similar in patients and controls, (i) sHLA-G levels were increased in EOC independent of the haplotype, (ii) homozygosity for UTR-1 or UTR-2 genotypes were significantly associated with metastases formation and presence of circulating tumor cells before therapy, whereas (iii) the UTR-5 and UTR-7 haplotypes were significantly associated with a beneficial clinical outcome regarding negative nodal status, early FIGO staging, and improved overall survival. Lastly, (iv) the ambivalent impact on clinical EOC aspects could be deduced to specific SNPs in the HLA-G 3′UTR: +3187G, +3196G and +3035T alleles. Our results give evidence that even if the genetic background of the HLA-G 3′UTR is identical between patients and controls, certain SNPs have the potential to contribute to diametrical clinical status/outcome in EOC.

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The impact of HLA-G 3′ UTR variants and sHLA-G on risk and clinical correlates of schizophrenia

Cited by 15 publications

References 51 publications

The association of HLA-G polymorphisms and the synergistic effect of sMICA and sHLA-G with chronic kidney disease and allograft acceptance

The association of HLA-G polymorphisms and the synergistic effect of sMICA and sHLA-G with chronic kidney disease and allograft acceptance

The Etiology of Auditory Hallucinations in Schizophrenia: From Multidimensional Levels

HLA-G 3′ untranslated region variants +3187G/G, +3196G/G and +3035T define diametrical clinical status and disease outcome in epithelial ovarian cancer

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