Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients

Takashi Higuchi; Shomi Oka; Hiroshi Furukawa; Kota Shimada; Atsushi Hashimoto; Akiko Komiya; Toshihiro Matsui; Naoshi Fukui; Shigeto Tohma

doi:10.3390/genes14071470

Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients

Genes (Basel). 2023 Jul 19;14(7):1470. doi: 10.3390/genes14071470.

Authors

Takashi Higuchi^{1

2}, Shomi Oka^{1

3}, Hiroshi Furukawa^{1

3}, Kota Shimada^{4

5}, Atsushi Hashimoto^{4

6}, Akiko Komiya^{3

7}, Toshihiro Matsui^{3

4}, Naoshi Fukui^{3

8}, Shigeto Tohma^{1

3}

Affiliations

¹ Department of Rheumatology, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose 204-8585, Japan.
² Department of Nephrology, Ushiku Aiwa General Hospital, 896 Shishiko-cho, Ushiku 300-1296, Japan.
³ Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan.
⁴ Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan.
⁵ Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashi-dai, Fuchu 183-8524, Japan.
⁶ Department of Internal Medicine, Sagami Seikyou Hospital, 6-2-11 Sagamiohno, Minami-ku, Sagamihara 252-0303, Japan.
⁷ Department of Clinical Laboratory, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan.
⁸ Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.

Abstract

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients.

Methods: HLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m²]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m²]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients.

Results: There was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09-2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24-2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics.

Conclusions: The present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear.

Keywords: HLA; chronic kidney disease; rheumatoid arthritis.

Publication types

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

MeSH terms

Arthritis, Rheumatoid* / complications
Arthritis, Rheumatoid* / genetics
East Asian People
Genetic Predisposition to Disease
HLA-DRB1 Chains / genetics
Humans
Renal Insufficiency, Chronic* / genetics

Substances

HLA-DRB1 Chains

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (B, C) (26293123, 22591090, 15K09543, 18K08402) and for Young Scientists (B) (24791018) from the Japan Society for the Promotion of Science, Health and Labour Science Research Grants from the Ministry of Health, Labour, and Welfare of Japan, Grants-in-Aid of the Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development, Grants-in-Aid for Clinical Research from National Hospital Organization, Research Grants from Daiwa Securities Health Foundation, Research Grants from Japan Research Foundation for Clinical Pharmacology, Research Grants from The Nakatomi Foundation, Research Grants from Takeda Science Foundation, Research Grants from Mitsui Sumitomo Insurance Welfare Foundation, Bristol-Myers K.K., RA Clinical Investigation Grant from Bristol-Myers Squibb Co., and research grants from the following pharmaceutical companies: Abbott Japan Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsuibishi Tanabe Pharma Corporation, Merck Sharp and Dohme Inc., Pfizer Japan Inc., Takeda Pharmaceutical Company Limited, and Teijin Pharma Limited. The funders had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript.