PMID- 24929145 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20140804 IS - 1879-1166 (Electronic) IS - 0198-8859 (Linking) VI - 75 IP - 8 DP - 2014 Aug TI - HLA-G gene expression influenced at allelic level in association with end stage renal disease and acute allograft rejection. PG - 833-9 LID - S0198-8859(14)00169-4 [pii] LID - 10.1016/j.humimm.2014.06.005 [doi] AB - BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major-histocompatibility complex class-I molecule associated with immunosuppressive function. We have evaluated the impact of HLA-G allele associated with untranslated-region (UTR)-haplotype in end stage renal disease (ESRD) and acute allograft rejection (AR) cases. The mRNA levels of different HLA-G isoforms were evaluated in ESRD and AR cases. Subsequently, the total HLA-G mRNA levels and protein concentration were evaluated against its UTR-haplotype among ESRD and AR cases. METHODOLOGY: Sequence based typing of the promoter region was carried-out to evaluate the impact of HLA-G haplotype in 350 ESRD cases and 300 controls. HLA-G gene expression was evaluated at the transcriptional level using semi-quantitative and quantitative PCR, whereas protein concentration was determined by ELISA among both cases and control. RESULTS: Increased risk was observed for G*01:01:01:03, G*01:01:02, G*01:06 and G*01:05:N haplotypes while G*01:01:01:01 and G*01:04:01 haplotypes showed a protective effect in ESRD and AR cases. Higher level of soluble HLA-G isoforms (G5 and G6) was observed among ESRD cases. Reduced levels of soluble isoform (G5) and increased levels of membrane bound (G1 and G3) isoforms were found among AR cases, revealing risk association. Decreased HLA-G expression was observed at both mRNA and protein level for G*01:01:01:03 and G*01:05:N haplotypes in ESRD and AR cases. CONCLUSIONS: These results suggest that the variation in the expression profile of membrane bound and soluble isoforms may modulate the risk for ESRD and AR. UTR-haplotypes appear to be involved in different HLA-G expression patterns at transcriptional and translational levels. CI - Copyright (c) 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. FAU - Misra, Maneesh Kumar AU - Misra MK AD - Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India; Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India. FAU - Pandey, Shashi Kant AU - Pandey SK AD - Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India. FAU - Kapoor, Rakesh AU - Kapoor R AD - Department of Urology and Renal Transplantation, SGPGIMS, Lucknow 226014, UP, India. FAU - Sharma, Raj Kumar AU - Sharma RK AD - Department of Nephrology, SGPGIMS, Lucknow 226014, UP, India. FAU - Kapoor, Rohit AU - Kapoor R AD - Department of Surgery, Era's Lucknow Medical College and Hospital, Lucknow 226003, India. FAU - Prakash, Swayam AU - Prakash S AD - Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India. FAU - Agrawal, Suraksha AU - Agrawal S AD - Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India. Electronic address: sur_ksha_agrawal@yahoo.co.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140611 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (HLA-G Antigens) RN - 0 (Protein Isoforms) SB - IM MH - Acute Disease MH - Adult MH - Alleles MH - Case-Control Studies MH - Female MH - Gene Expression MH - Gene Frequency MH - Graft Rejection/*genetics/immunology/pathology MH - HLA-G Antigens/*genetics/immunology MH - Haplotypes MH - Humans MH - Kidney Failure, Chronic/*genetics/immunology/pathology/surgery MH - *Kidney Transplantation MH - Male MH - Middle Aged MH - *Promoter Regions, Genetic MH - Protein Isoforms/genetics/immunology MH - Risk MH - Solubility MH - Transplantation, Homologous OTO - NOTNLM OT - Acute allograft rejection OT - End stage renal disease OT - HLA-G allele OT - HLA-G expression OT - UTR haplotype EDAT- 2014/06/15 06:00 MHDA- 2015/03/31 06:00 CRDT- 2014/06/15 06:00 PHST- 2013/11/12 00:00 [received] PHST- 2014/06/03 00:00 [revised] PHST- 2014/06/03 00:00 [accepted] PHST- 2014/06/15 06:00 [entrez] PHST- 2014/06/15 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - S0198-8859(14)00169-4 [pii] AID - 10.1016/j.humimm.2014.06.005 [doi] PST - ppublish SO - Hum Immunol. 2014 Aug;75(8):833-9. doi: 10.1016/j.humimm.2014.06.005. Epub 2014 Jun 11.