TY - JOUR
T1 - Human leukocyte antigen associations with renal function among ethnic minorities in the United Kingdom
AU - Lowe, Marcus
AU - Payton, Antony
AU - Verma, Arpana
AU - Gemmell, Isla
AU - Worthington, Judith
AU - Hamilton, Patrick
AU - Ollier, William
AU - Augustine, Titus
AU - Poulton, Kay
N1 - Funding Information:
Data was provided by UK Biobank. Funding was provided by Kidneys for Life. Data cannot be shared as access is restricted to individuals named on the application to UK Biobank.
Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - HLA antigens
KW - genome-wide association study
KW - glomerular filtration rate
KW - imputation
KW - kidney failure, chronic
KW - polymorphism, single nucleotide
KW - renal insufficiency
U2 - 10.1111/tan.14078
DO - 10.1111/tan.14078
M3 - Article
C2 - 32985786
VL - 96
SP - 697
EP - 708
JO - HLA
JF - HLA
SN - 2059-2302
IS - 6
ER -
