Associations between human leukocyte antigens and renal function

Sci Rep. 2021 Feb 4;11(1):3158. doi: 10.1038/s41598-021-82361-7.

Abstract

Human leukocyte antigens (HLA) have been associated with renal function, but previous studies report contradictory findings with little consensus on the exact nature or impact of this observation. This study included 401,307 white British subjects aged 39-73 when they were recruited by UK Biobank. Subjects' HLA types were imputed using HLA*IMP:02 software. Regression analysis was used to compare 362 imputed HLA types with estimated glomerular filtration rate (eGFR) as a primary outcome and clinical indications as secondary outcome measures. 22 imputed HLA types were associated with increased eGFR (and therefore increased renal function). Decreased eGFR (decreased renal function) was associated with 11 imputed HLA types, seven of which were also associated with increased risk of end-stage renal disease and/or chronic kidney disease. Many of these HLA types are commonly inherited together in established haplotypes, for example: HLA-A*01:01, B*08:01, C*07:01, DRB1*03:01, DQB1*02:01. This haplotype has a population frequency of 9.5% in England and each allele was associated with decreased renal function. 33 imputed HLA types were associated with kidney function in white British subjects. Linkage disequilibrium in HLA heritance suggests that this is not random and particularly affects carriers of established haplotypes. This could have important applications for the diagnosis and treatment of renal disease and global population health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Biological Specimen Banks
  • England / epidemiology
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Glomerular Filtration Rate
  • HLA Antigens / classification
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Haplotypes*
  • Heterozygote
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / physiopathology
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / immunology
  • Renal Insufficiency, Chronic / physiopathology

Substances

  • HLA Antigens