Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease.
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Namkoong Ho, Omae Yosuke, Asakura Takanori, Ishii Makoto, Suzuki Shoji, Morimoto Kozo, Kawai Yosuke, Emoto Katsura, Oler Andrew J, Szymanski Eva P, Yoshida Mitsunori, Matsuda Shuichi, Yagi Kazuma, Hase Isano, Nishimura Tomoyasu, Sasaki Yuka, Asami Takahiro, Shiomi Tetsuya, Matsubara Hiroaki, Shimada Hisato, Hamamoto Junko, Jhun Byung Woo, Kim Su-Young, Huh Hee Jae, Won Hong-Hee, Ato Manabu, Kosaki Kenjiro, Betsuyaku Tomoko, Fukunaga Koichi, Kurashima Atsuyuki, Tettelin Hervé, Yanai Hideki, Mahasirimongkol Surakameth, Olivier Kenneth N, Hoshino Yoshihiko, Koh Won-Jung, Holland Steven M, Tokunaga Katsushi, Hasegawa Naoki, Nontuberculous Mycobacteriosis and Bronchiectasis – Japan Research Consortium (NTM-JRC)
Аннотация
OBJECTIVES: We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen.
METHODS: This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping.
RESULTS: The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10-13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10-12, OR 0.54) and European (p=5.12×10-03, OR 0.63) ancestry.
CONCLUSIONS: We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.