Effect of telomere length and TERT/TERC rare variants on survival in Japanese patients with idiopathic interstitial pneumonias：Genetic predisposition study from the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (NEJ036A)

<bold>Rationale:</bold> While genetic research on pulmonary fibrosis has primarily been conducted in Western populations, there is a paucity of data regarding Asian populations. This study aims to elucidate the relationship between genomic biomarkers and survival among Japanese patients with idiopathic interstitial pneumonias (IIPs). <bold>Methods:</bold> 450 patients from the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (total n=866) were enrolled in a separate genetic predisposition study (NEJ036A). This study investigated single nucleotide polymorphisms in genes including <italic>MUC5B</italic>, <italic>TERT</italic>, <italic>TERC</italic>, and <italic>TOLLIP</italic>, as well as rare variants (RVs) in <italic>TERT</italic>/<italic>TERC</italic>. Leukocyte telomere length (LTL) was measured using Southern blot analysis. The Cox hazard regression model was utilized to analyze the association between genetic predisposition and survival. <bold>Results:</bold> Age-adjusted LTL below the median (LTL < 50%) and RVs in <italic>TERT</italic>/<italic>TERC</italic> were significantly associated with poorer transplant-free survival (LTL: HR 2.61 [95% CI 1.68-4.05], P < 0.0001; RVs: HR 3.99 [95% CI 1.43-11.15], P = 0.0082), independently of age, sex, %FVC, %DLCO, and IPF diagnosis. Shorter LTL was linked to increased mortality in both IPF and non-IPF patients, with those having LTL<50% experiencing accelerated declines in FVC and DLCO. <bold>Conclusions:</bold> In Japanese patients with IIPs, shorter LTL and RVs in <italic>TERT</italic>/<italic>TERC</italic> are associated with reduced survival, paralleling findings observed in Western populations. This emphasizes the critical role of telomere biology in pulmonary fibrosis across diverse ethnic groups.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.oa2867
Primary Topic
Telomeres, Telomerase, and Senescence
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article
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article

Effect of telomere length and TERT/TERC rare variants on survival in Japanese patients with idiopathic interstitial pneumonias：Genetic predisposition study from the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (NEJ036A)

Koji Sakamoto, Shu Hisata, Takuma Isshiki, Koichi Hagiwara et al.
Telomeres, Telomerase, and Senescence
article

Effect of telomere length and TERT/TERC rare variants on survival in Japanese patients with idiopathic interstitial pneumonias：Genetic predisposition study from the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (NEJ036A)

Koji Sakamoto, Shu Hisata, Takuma Isshiki, Koichi Hagiwara, Mikio Toyoshima, Shizukiyo Ishikawa, Makiko Mieno, Noboru Hattori, Yukihiro Horio, Yasuhiko Nishioka, Yoshinori Tanino, Yasuhiro Kondoh, Ryo Okuda, Toru Arai, Motoyasu Kato, Kunihiko Kobayashi, Hiromi Tomioka, Mitsuhiro Abe, Hirofumi Chiba, Naoki Hamada, Yasunari Miyazaki, Tomoaki Hoshino, Takuji Suzuki, Yasuo Shimizu, Haruyuki Ishii, Motoaki Tanigawa, Yasushi Horimasu, Nobuhisa Ishikawa, Tomohisa Baba, Takashi Ogura, Takafumi Suda, Naoki Arai, Toshihiro Nukiwa, Yukari Tsubata
article en

Abstract

<bold>Rationale:</bold> While genetic research on pulmonary fibrosis has primarily been conducted in Western populations, there is a paucity of data regarding Asian populations. This study aims to elucidate the relationship between genomic biomarkers and survival among Japanese patients with idiopathic interstitial pneumonias (IIPs). <bold>Methods:</bold> 450 patients from the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry (total n=866) were enrolled in a separate genetic predisposition study (NEJ036A). This study investigated single nucleotide polymorphisms in genes including <italic>MUC5B</italic>, <italic>TERT</italic>, <italic>TERC</italic>, and <italic>TOLLIP</italic>, as well as rare variants (RVs) in <italic>TERT</italic>/<italic>TERC</italic>. Leukocyte telomere length (LTL) was measured using Southern blot analysis. The Cox hazard regression model was utilized to analyze the association between genetic predisposition and survival. <bold>Results:</bold> Age-adjusted LTL below the median (LTL < 50%) and RVs in <italic>TERT</italic>/<italic>TERC</italic> were significantly associated with poorer transplant-free survival (LTL: HR 2.61 [95% CI 1.68-4.05], P < 0.0001; RVs: HR 3.99 [95% CI 1.43-11.15], P = 0.0082), independently of age, sex, %FVC, %DLCO, and IPF diagnosis. Shorter LTL was linked to increased mortality in both IPF and non-IPF patients, with those having LTL<50% experiencing accelerated declines in FVC and DLCO. <bold>Conclusions:</bold> In Japanese patients with IIPs, shorter LTL and RVs in <italic>TERT</italic>/<italic>TERC</italic> are associated with reduced survival, paralleling findings observed in Western populations. This emphasizes the critical role of telomere biology in pulmonary fibrosis across diverse ethnic groups.

Kurume University (JP), Tokyo Medical and Dental University (JP), Toho University (JP), Fukushima Medical University (JP), Tokai University (JP), Sendai University (JP), Hamamatsu University (JP), Sapporo Medical University (JP), Jichi Medical University (JP), Shohoku College (JP), Chiba University (JP), Shimane University (JP), Kyorin University (JP), Hamamatsu University School of Medicine (JP), Juntendo University (JP), Fukuoka University Hospital (JP), Toho University Omori Medical Center (JP), Hiroshima Prefectural Hospital (JP), Hamamatsu Rosai Hospital (JP), Hiroshima University Hospital (JP), Saitama International Medical Center (JP), Ibarakihigashi National Hospital (JP), Kobe City Medical Center West Hospital (JP), Kanagawa Cardiovascular and Respiratory Center (JP), Ise Red Cross Hospital (JP), Jichi Medical University Hospital (JP), Tosei General Hospital (JP), NHO Kinki Chuo Chest Medical Center (JP), Nagoya University (JP), Dokkyo Medical University (JP), Saitama Medical University (JP), Tokushima University (JP)
Openalex Percentile: Top 72%
Telomeres, Telomerase, and Senescence
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