title: HLA-G gene expression influenced at allelic level in association with end stage renal disease and acute allograft rejection.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Misra
authors.affiliation: Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India.
authors.forename: Shashi Kant
authors.initials: SK
authors.lastname: Pandey
authors.affiliation: Department of Urology and Renal Transplantation, SGPGIMS, Lucknow 226014, UP, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.affiliation: Department of Nephrology, SGPGIMS, Lucknow 226014, UP, India.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Department of Surgery, Era's Lucknow Medical College and Hospital, Lucknow 226003, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Kapoor
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India.
authors.forename: Swayam
authors.initials: S
authors.lastname: Prakash
authors.affiliation: 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.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000208:Acute Disease; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D059951:HLA-G Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012306:Risk; D012995:Solubility; D014184:Transplantation, Homologous
chemical_list: D059951:HLA-G Antigens; D020033:Protein Isoforms
keywords: Acute allograft rejection; End stage renal disease; HLA-G allele; HLA-G expression; UTR haplotype