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

Author:

Higuchi Takashi12,Oka Shomi13,Furukawa Hiroshi13ORCID,Shimada Kota45,Hashimoto Atsushi46,Komiya Akiko37,Matsui Toshihiro34,Fukui Naoshi38,Tohma Shigeto13

Affiliation:

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.

Funder

Japan Society for the Promotion of Science

the Ministry of Health, Labour, and Welfare of Japan

Japan Agency for Medical Research and Development

National Hospital Organization

Daiwa Securities Health Foundation

Japan Research Foundation for Clinical Pharmacology

The Nakatomi Foundation

Takeda Science Foundation

Mitsui Sumitomo Insurance Welfare Foundation

Bristol-Myers Squibb Co.

Abbott Japan Co., Ltd.

Bristol-Myers K.K.

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

Teijin Pharma Limited

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

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