Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 23;7(8):e737.
doi: 10.1097/TXD.0000000000001188. eCollection 2021 Aug.

HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes

Nuvreen Phagura  1 , Azm Hussain  2 , Alice Culliford  2 , James Hodson  3 , Felicity Evison  4 , Suzy Gallier  4   5 , Richard Borrows  2 , Hanna A Lane  6 , David Briggs  6 , Adnan Sharif  2   7
Affiliations

HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes

Nuvreen Phagura et al. Transplant Direct. .

Abstract

The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods: In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results: PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001).

Conclusion: Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.

PubMed Disclaimer

Conflict of interest statement

The authors declare no funding or conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Kaplan–Meier curve of PTDM. PTDM, posttransplantation diabetes.
FIGURE 2.
FIGURE 2.
Kaplan–Meier curve of PTDM stratified by (A) HLA Cw12, (B) HLA B58, and (C) HLA DQ4 status. PTDM, posttransplantation diabetes.
FIGURE 3.
FIGURE 3.
Kaplan–Meier curve of PTDM by recipient ethnicity and HLA B58 status. PTDM, posttransplantation diabetes.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Sharif A, Cohney S. Post-transplantation diabetes-state of the art. Lancet Diabetes Endocrinol. 2016;4:337–349. - PubMed
    1. Sharif A, Hecking M, de Vries AP, et al. . Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant. 2014;14:1992–2000. - PMC - PubMed
    1. Sharif A, Baboolal K. Risk factors for new-onset diabetes after kidney transplantation. Nat Rev Nephrol. 2010;6:415–423. - PubMed
    1. Rich SS. Mapping genes in diabetes. Genetic epidemiological perspective. Diabetes. 1990;39:1315–1319. - PubMed
    1. Gaulton KJ, Ferreira T, Lee Y, et al. ; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat Genet. 2015;47:1415–1425. - PMC - PubMed