PMID- 24131018 OWN - NLM STAT- MEDLINE DCOM- 20140620 LR - 20131017 IS - 1399-0039 (Electronic) IS - 0001-2815 (Linking) VI - 82 IP - 5 DP - 2013 Nov TI - Association of HLA-G promoter and 14-bp insertion-deletion variants with acute allograft rejection and end-stage renal disease. PG - 317-26 LID - 10.1111/tan.12210 [doi] AB - The aim of this study was to investigate the HLA-G 14-bp insertion/deletion (I/D) polymorphism among end-stage renal disease (ESRD) patients. Cytomegalovirus (CMV) infection, acute allograft rejection (AR) and overall survival after renal transplantation was investigated in 300 ESRD patients and 302 age, sex and ethnicity-matched controls. Sequencing was performed to evaluate the impact of HLA-G promoter region single-nucleotide polymorphisms (SNPs) whereas semi-quantitative PCR method was used to determine the probable HLA-G expression pattern among ESRD and AR cases. Further, soluble human leukocyte antigen (HLA)-G (sHLA-G) expression levels were compared in AR vs non-AR cases in the light of HLA-G 14-bp I/D polymorphism. Increased risk was found for 14-bp D/D (deletion-DD) genotype and 14-bp D allele [DD: odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.03-2.06, P value = 0.0358; D: OR = 1.29, 95% CI = 1.03-1.62, P value = 0.0277], respectively for ESRD and CMV infection (DD: OR = 2.70, 95% CI = 1.45-5.05, P value = 0.0021; D: OR = 1.94, 95% CI = 1.22-3.08, P value = 0.0052). Nearly fourfold (OR = 3.62, 95%CI = 1.61-8.14, p = 0.0039) risk was observed for 14-bp I/I (insertion-II) genotype for AR. Survival analysis showed increased overall survival (OS) (AR or death) for 14-bp D/D genotype. HLA-G promoter region sequencing was carried out among 60 ESRD patients and 100 normal controls which showed increased risk for -964 G>A, -725 C>G/T and -486 A>C SNPs. -964 G>A and -725 C>G/T SNPs showed risk association for AR patients. High level of HLA-G transcripts was observed among non-AR patients. Further soluble HLA-G (sHLA-G) showed increased levels in ESRD patients (mean +/- SEM; 62.16 +/- 2.43 U/ml) as compared to controls (mean +/- SEM; 21.06 +/- 3.89 U/ml) (P = <0.0001). The 14-bp I/I, 14-bp I/D and 14-bp D/D genotypes showed significantly higher levels of sHLA-G among non-AR as compared to AR patients. CI - (c) 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Misra, M K AU - Misra MK AD - Department of Medical genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow, India; Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. FAU - Prakash, S AU - Prakash S FAU - Kapoor, R AU - Kapoor R FAU - Pandey, S K AU - Pandey SK FAU - Sharma, R K AU - Sharma RK FAU - Agrawal, S AU - Agrawal S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (HLA-G Antigens) SB - IM MH - Allografts/*metabolism MH - Base Pairing/genetics MH - Cytomegalovirus Infections/complications/genetics MH - Demography MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Frequency MH - *Genetic Association Studies MH - Genetic Predisposition to Disease MH - Graft Rejection/complications/*genetics MH - HLA-G Antigens/*genetics MH - Humans MH - INDEL Mutation/*genetics MH - Kaplan-Meier Estimate MH - Kidney Failure, Chronic/complications/*genetics MH - Linkage Disequilibrium/genetics MH - Male MH - Promoter Regions, Genetic/*genetics MH - Solubility OTO - NOTNLM OT - HLA-G 14-bp insertion/deletion OT - HLA-G 5' URR OT - acute allograft rejection OT - cytomegalovirus infection OT - end-stage renal disease OT - soluble HLA-G EDAT- 2013/10/18 06:00 MHDA- 2014/06/21 06:00 CRDT- 2013/10/18 06:00 PHST- 2012/12/27 00:00 [received] PHST- 2013/08/27 00:00 [revised] PHST- 2013/09/06 00:00 [accepted] PHST- 2013/10/18 06:00 [entrez] PHST- 2013/10/18 06:00 [pubmed] PHST- 2014/06/21 06:00 [medline] AID - 10.1111/tan.12210 [doi] PST - ppublish SO - Tissue Antigens. 2013 Nov;82(5):317-26. doi: 10.1111/tan.12210.