Truncating Variants in OBSCN Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy

Author:

Wu Guixin12ORCID,Liu Jie12ORCID,Liu Minghao2,Huang Qiya12,Ruan Jieyun12ORCID,Zhang Channa1,Wang Dong2,Sun Xiaolu2,Jiang Wen2,Kang Lianming2,Wang Jizheng1ORCID,Song Lei123ORCID

Affiliation:

1. State Key Laboratory of Cardiovascular Disease (G.W., J.L., Q.H., J.R., C.Z., J.W., L.S.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

2. Cardiomyopathy Ward (G.W., J.L., M.L., Q.H., J.R., D.W., X.S., W.J., L.K., L.S.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

3. National Clinical Research Center of Cardiovascular Diseases (L.S.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: The presence of variants in OBSCN was identified to be linked to hypertrophic cardiomyopathy (HCM), but whether OBSCN truncating variants were associated with HCM remained unknown. Methods: Whole-exome sequencing was performed in 986 patients with HCM and 761 non-HCM controls to search for OBSCN truncating variants, and the result was tested in a replication cohort consisting of 529 patients with HCM and 307 controls. The association of the OBSCN truncating variants with baseline characteristics and prognosis of patients with HCM were ascertained. Results: There were 28 qualifying truncating variants in the OBSCN gene detected in 26 (2.6%) patients with HCM and 6 (0.8%) controls. The OBSCN truncating variants were more prevalent in patients with HCM than controls (odds ratio, 3.4, P =0.004). This association was confirmed in the replication cohort (odds ratio, 3.8, P =0.024). The combined effects of the two cohorts estimated the odds ratio to be 3.58 ( P <0.001). Patients with or without OBSCN truncating variants shared similar demographic and echocardiographic variables at baseline. During 3.3±2.4 years (4795 patient-years) follow-up, the patients with OBSCN truncating variants were more likely to experience cardiovascular death (adjusted hazard ratio, 3.1 [95% CI, 1.40–6.70], P =0.005) and all-cause death (adjusted hazard ratio, 2.63 [95% CI, 1.21–5.71], P =0.015). Conclusions: Our data indicated that OBSCN truncating variants contributed to the disease-onset of HCM, and increased the risk of malignant events in patients with HCM.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine

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