Human leukocyte antigen associations with renal function among ethnic minorities in the United Kingdom

Marcus Lowe; Antony Payton; Arpana Verma; Isla Gemmell; Judith Worthington; Patrick Hamilton; William Ollier; Titus Augustine; Kay Poulton

doi:10.1111/tan.14078

Human leukocyte antigen associations with renal function among ethnic minorities in the United Kingdom

HLA. 2020 Dec;96(6):697-708. doi: 10.1111/tan.14078. Epub 2020 Nov 5.

Authors

Marcus Lowe^{1

2}, Antony Payton³, Arpana Verma², Isla Gemmell², Judith Worthington¹, Patrick Hamilton⁴, William Ollier^{2

5}, Titus Augustine^{4

6}, Kay Poulton^{1

2}

Affiliations

¹ Transplantation Laboratory, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK.
² Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.
³ Faculty of Biology, Medicine and Health, Division of Informatics, Imaging & Data Sciences, School of Health Sciences, University of Manchester, Manchester, UK.
⁴ Department of Renal and Pancreas Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK.
⁵ Faculty of Science and Engineering, Centre for Bioscience, Manchester Metropolitan University, Manchester, UK.
⁶ Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK.

PMID: 32985786
DOI: 10.1111/tan.14078

Abstract

Human leukocyte antigens (HLA) have been associated with renal function, but previous studies report contradictory findings. There has been a lack of research into how HLA affects renal function in Black, Asian and Minority Ethnic (BAME) people in the UK, despite BAME people being disproportionately affected by renal dysfunction. This study included >27 000 UK Biobank subjects of six ethnicities (>12 100 Irish, >5400 Indian, >4000 Black Caribbean, >3000 Black African, >1600 Pakistani, and >1400 Chinese) aged 39 to 73. Subjects' high-resolution HLA genotypes were imputed using HLA*IMP:02 software. Regression analysis was used to compare 108 imputed HLA alleles with two measures of estimated glomerular filtration rate (eGFR): one based on serum creatinine; one based on serum cystatin. Secondary analysis compared CKD stage 2 subjects to healthy controls. Nine imputed HLA alleles were associated with eGFR (adjusted P < .05). Six associations were based on creatinine in Black African subjects: HLA-B*53:01 (beta = -2.628, adjusted P = 4.69 × 10^-4 ); C*04:01 (beta = -1.667, adjusted P = .0269); DPA1*02:01 (beta = -1.569, adjusted P = .0182); and DPA1*02:02 (beta = -1.716, adjusted P = .0251) were linked to decreased renal function, while DRB1*03:01 (beta = 3.200, adjusted P = 3.99 × 10^-3 ) and DPA1*01:03 (beta = 2.276, adjusted P = 2.31 × 10^-5 ) were linked to increased renal function. Two of these (HLA-B*53:01 and C*04:01) are commonly inherited together. In Irish subjects, HLA-DRB1*04:01 (beta = 1.075, adjusted P = .0138) was linked to increased eGFR (based on cystatin); in Indian subjects, HLA-DRB1*03:01 (beta = -1.72, adjusted P = 4.78 × 10^-3 ) and DQB1*02:01 (beta = -1.755, adjusted P = 2.26 × 10^-3 )were associated with decreased eGFR (based on cystatin). No associations were found in the other three ethnic groups. Nine HLA alleles appear to be associated with kidney function in BAME people in the UK. This could have applications for the diagnosis and treatment of renal disease and could help reduce health inequalities in the UK.

Keywords: HLA antigens; genome-wide association study; glomerular filtration rate; imputation; kidney failure, chronic; polymorphism, single nucleotide; renal insufficiency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Ethnicity* / genetics
Gene Frequency
HLA Antigens / genetics
HLA-DQ beta-Chains / genetics
HLA-DRB1 Chains / genetics
Haplotypes
Histocompatibility Antigens Class I* / genetics
Humans
United Kingdom

Substances

HLA Antigens
HLA-DQ beta-Chains
HLA-DRB1 Chains
Histocompatibility Antigens Class I