Interferon regulatory factor 5 polymorphisms in sarcoidosis

Abstract

Objective Interferon regulatory factor 5 (IRF5) gene polymorphisms are associated with susceptibility to autoimmune diseases. The aim of this study is to determine the roles of IRF5 single-nucleotide polymorphisms (SNPs) in sarcoidosis.

Methods A total of 175 Japanese patients with biopsy-proven sarcoidosis and 150 sex-matched controls were genotyped for four IRF5 SNPs: rs729302A/C, rs2004640G/T, rs10954213A/G, and rs2280714G/A. The associations of these SNPs with susceptibility to sarcoidosis were examined.

Results Carriage of rs10954213A and rs2280714A conferred significant risks for sarcoidosis [carriage of rs10954213A: odds ratio (OR) = 1.96, 95 % confidence interval (CI) = 1.15–3.33, P = 0.01, corrected P = 0.04; carriage of rs2280714A: OR = 1.97, 95 % CI = 1.22–3.16, P = 0.005, corrected P = 0.02]. The haplotype carrying rs10954213A and rs2280714A (haplotype 2) was significantly associated with susceptibility to sarcoidosis (OR = 2.00, 95 % CI = 1.24–3.24, P = 0.004, corrected P = 0.01). rs729302 and rs2004640 were not associated with susceptibility to sarcoidosis, whereas carriage of rs2004640G was protective against pulmonary hypertension (OR = 0.017, 95 % CI = 0.002–0.15, P < 0.001, corrected P < 0.001).

Conclusion A haplotype carrying two functional SNPs of IRF5, rs10954213A and rs2280714A, was associated with the risk of sarcoidosis in the Japanese population.

Keywords::

• Interferon regulatory factor 5
• Haplotype
• Pulmonary hypertension
• Sarcoidosis
• Single-nucleotide polymorphism

Acknowledgments

We thank Dr. S. Kadowaki (Ono Municipal Hospital) for assistance with collecting control samples. We thank Professor K. Chin (Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University) for academic advice. We thank Ms. Y. Sato, Ms. M. Yokota, and Ms. S. Yoshida for help in the outpatient clinic and Ms. H. Inoue, Ms. Y. Kubo, Ms. I. Morioka, Ms. S. Shima, and Ms. N. Chaki for secretarial help. We also thank Mr. S. Ueda, Ms. N. Matsuzaki, and Ms. M. Nakatsuji for technical assistance, Ms. Maeda for laboratory work, and Ms. T. Toki and Ms. M. Sotoda for help with manuscript preparation. This study was supported by grants from the Respiratory Failure Study Group and Diffuse Lung Disease Study Group from the Ministry of Health, Labor, and Welfare, Japan.

Conflicts of interest

None.