UCP2 polymorphisms, daily step count, and number of teeth associated with all-cause mortality risk in Sado City: A hospital-based cohort study

Han Lyu; Noriko Sugita; Shigeki Komatsu; Minako Wakasugi; Akio Yokoseki; Akihiro Yoshihara; Tetsuo Kobayashi; Kenji Sato; Hiroyuki Kawashima; Osamu Onodera; Ichiei Narita; Koichi Tabeta

doi:10.1016/j.heliyon.2024.e32512

UCP2 polymorphisms, daily step count, and number of teeth associated with all-cause mortality risk in Sado City: A hospital-based cohort study

Heliyon. 2024 Jun 8;10(12):e32512. doi: 10.1016/j.heliyon.2024.e32512. eCollection 2024 Jun 30.

Authors

Affiliations

¹ Division of Periodontology, Department of Oral Biological Science, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
² Sado General Hospital, Niigata, Japan.
³ Department of Inter-Organ Communication Research, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁴ Division of Oral Science and Health Promotion, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
⁵ General Dentistry and Clinical Education Unit, Faculty of Dentistry & Medical and Dental Hospital, Niigata University, Niigata, Japan.
⁶ Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
⁷ Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
⁸ Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Abstract

Objective: Uncoupling protein 2 (UCP2) is an ion/anion transporter in the mitochondrial inner membrane that plays a crucial role in immune response, regulation of oxidative stress, and cellular metabolism. UCP2 polymorphisms are linked to chronic inflammation, obesity, diabetes, heart disease, exercise efficiency, and longevity. Daily step count and number of teeth are modifiable factors that reduce mortality risk, although the role of UCP2 in this mechanism is unknown. This study aimed to assess the possible effects of UCP2 polymorphisms on the association between daily step count and number of teeth with all-cause mortality.

Methods: This study was conducted as a cohort project involving adult Japanese outpatients at Sado General Hospital (PROST). The final number of participants was 875 (mean age: 69 y). All-cause mortality during thirteen years (from June 2008 to August 2021) was recorded. The functional UCP2 genotypes rs659366 and rs660339 were identified using the Japonica Array®. Survival analyses were performed using multivariate Cox proportional hazard models.

Results: There were 161 deaths (mean observation period: 113 months). Age, sex, daily step count, and the number of teeth were significantly associated with mortality. In females, UCP2 polymorphisms were associated with mortality independent of other factors (rs659366 GA compared to GG + AA; HR = 2.033, p = 0.019, rs660339 C T compared to CC + TT; HR = 1.911, p = 0.029). Multivariate models, with and without UCP2 genotypes, yielded similar results. The interaction terms between UCP2 genotype and daily step count or number of teeth were not significantly associated with mortality.

Conclusion: The effects of UCP2 polymorphisms on the association between daily step count or the number of teeth and all-cause mortality were not statistically significant. In females, UCP2 polymorphisms were significantly associated with all-cause mortality. Our findings confirmed the importance of physical activity and oral health and suggested a role of UCP2 in mortality risk independently with those factors.

Keywords: Epidemiology; Genetic; Mitochondria; Oral health; Physical activity.