A common mutation of the MYH gene is associated with increased DNA oxidation and age-related diseases |
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| Authors: | Caixia Sun Huimei Chen Wenwen Guo Kui Zhang Qiufeng Qi Xin Gu Dalong Zhu Yaping Wang |
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| Institution: | 1. Department of Medical Genetics, Nanjing University School of Medicine, Nanjing 210093, China;2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China;3. Laboratory of Clinic Biochemistry, Medical School affiliated with Drum Tower Hospital, Nanjing University, Nanjing, China;4. Department of Endocrinology, Medical School affiliated with Drum Tower Hospital, Nanjing University, Nanjing, China;1. Research Division, Peter MacCallum Cancer Centre, East Melbourne, Australia;2. Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia;3. Centre for Biostatistics and Clinical Trial, Peter MacCallum Cancer Centre, East Melbourne, Australia;4. Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Australia;5. Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia;6. Department of Pathology, Royal Melbourne Hospital, Parkville, Australia;7. Department of Oral and Maxillofacial Surgery, Royal Melbourne Hospital, Parkville, Australia;8. Department of Otorhinolaryngology, Monash Medical Centre, Clayton, Australia;9. Department of Surgery, St. Vincent’s Hospital, Fitzroy, Australia;10. Department of Anatomical Pathology, St. Vincent’s Hospital, Fitzroy, Australia;11. University of Melbourne, Parkville, Australia;1. Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;2. Department of Human Anatomy, Chongqing Medical University, Chongqing 400016, China;3. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;1. Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;2. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan;3. Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan;5. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;6. Cancer Center, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;7. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;8. Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;9. Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan;10. Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital, Taipei, Taiwan;11. Division of Consultation and Promotion, Taiwan Drug Relief Foundation, Taipei, Taiwan;1. Department of Urology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China;2. Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China;1. Department of Geriatrics and Neurology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan;2. Department of Medical Genetics, Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan |
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| Abstract: | We describe a common mutation of the MYH gene, which is involved in the repair of oxidative damage to DNA, and its relationship to age, levels of 8-OHdG, and circulating levels of interleukin-1. We studied 1146 “healthy” and 562 unselected Chinese subjects. We observed a reverse insertion of the AluYb8 sequence (AluYb8MYH) to be homozygous in ～25.8% of the healthy Chinese population age 20–29 years, with the incidence of homozygosity decreasing to 15.7% by age 50–59 years. Because subjects were selected on the basis of absence of disease during medical screening, this suggests that homozygosity for this gene has a marked impact on the development of age-related or chronic diseases or mortality. Because the MYH gene is involved in DNA repair we assessed whether homozygous carriage of this gene was associated with increased levels of 8-OHdG in the leukocytic DNA of carriers. The level of 8-OHdG increased from 3.8 8-OHdG/106 dG in wild-type carriers to 10.8 8-OHdG/106 dG in homozygous carriers, suggesting that the presence of the mutation was associated with impaired DNA repair. Because this mutation might be associated with the increased development of age-related or chronic disease and inflammation, we also measured plasma concentrations of interleukin-1, which increases with aging and chronic disease. We observed a highly significant increase in plasma interleukin-1 in patients homozygous for the AluYb8 insertion in the MYH gene consistent with accelerated aging or development of undiagnosed disease in homozygous subjects. Screening for this genetic variation may have predictive value in assessing potential longevity of subjects in China, as well as in the Western world. |
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