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• W1978392275 abstract "To the Editor: Werner syndrome (WS) is an autosomal-recessive disorder caused by a mutation of the WNR gene and is considered to be a representative type of progeroid syndrome,1 which is highly prevalent in Japan. Because individuals with WS often have metabolic disorders and vascular complications, a nationwide epidemiological survey was initiated in Japan to clarify the current relationship between the prevalence of metabolic disorders and vascular complications in these individuals. The primary survey involved sending 6,000 survey sheets to hospitals with more than 200 beds. This survey confirmed 336 new patients. The secondary survey in 2011 involved sending questionnaires to hospitals that had responded to the primary survey. Detailed clinical data were obtained for 185 cases. Complication rates of metabolic disorder and morbidity from complications in individuals with WS were compared with those in the average Japanese population. Of the 185 patients, 86 were men, 98 were women, and the sex of one was unknown. The proportions of patients were 62.7% aged 50 to 59, 22.7% aged 40 to 49, 10.8% aged 30 to 39, 1.1% aged 20 to 29, and 0.5% aged 60 to 69, respectively. Mean height and body weight were 158.3 ± 8.6 cm and 45.3 ± 8.3 kg for 44 male patients and 148.5 ± 8.6 cm and 37.7 ± 8.3 kg for 94 female patients. The prevalence of diabetes mellitus and abnormal glucose tolerance were 55.7% and 6.5%, respectively, with a total combined rate of 62.2% (Table 1). Drugs used for diabetes mellitus included pioglitazone (10.3%), sulfonylurea (7.6%), insulin (7.0%), alpha-glucosidase inhibitor (5.9%), and metformin (4.9%). The morbidity of hyperlipidemia was 51.6%. Treatments for hyperlipidemia included statins (18.4%), fibrates (5.4%), and others (3.8%). The morbidity of hypertension was 25.9%, lower than that of the average Japanese population (Table 1). Therapeutic agents used were angiotensin II receptor antagonists (4.9%) and calcium blockers (4.3%). Morbidities of vascular diseases in WS were 1.1% for brain hemorrhage, 2.7% for cerebral infarction, 10.3% for angina pectoris or myocardial infarction, and 17.3% for arteriosclerosis obliterans. Individuals with WS were divided into two groups (with (n = 45) and without vascular disease (n = 140)), and correlations with diabetes mellitus (χ2 = 4.24, P = .04), hyperlipidemia (χ2 = 7.90, P = .005), and hypertension (χ2 = 11.16, P < .001) were examined, with a critical value of 3.84, confirming that metabolic disorders are closely related to vascular disease. This study confirmed a considerably higher prevalence of metabolic disorders and cardiovascular diseases in Japanese with WS than in the average Japanese population (Table 1). Because of the high prevalence of metabolic disorders, the accumulation of visceral fat tissue in WS has been attributed to the development of the metabolic syndrome,2 but the mechanisms underlying the accumulation of visceral fat tissue frequently observed in WS remains largely unknown. With regard to the characteristics of vascular disease in WS, the morbidity rate of stroke in individuals with WS was similar to that in the general Japanese population of the same age, although individuals with WS have a considerably greater prevalence of metabolic disorders. Stroke is more commonly caused by arteriolosclerosis than by atherosclerosis. Furthermore, arteriolosclerosis in the brain is associated with changes characterized by hyalinization of the tunica media or fibrinoid necrosis, which are closely associated with hypertension. The present survey demonstrated that the occurrence of hypertension as a complication of WS was lower than in the general Japanese population of the same ages; this has been a contributing factor to the smaller number of cerebral vascular disease in individuals with WS. In accordance with this lower incidence of cerebral vascular disturbances in individuals with WS, the function of the central nervous system is known to be maintained at a normal level, together with a lower incidence of dementia. Although the cause has not been clarified, the difference between the distribution of RecQ-type helicase (a protein that is mutated in WS) in vascular and cerebral blood vessels may be responsible. Furthermore, rapid cell division is associated with telomere stability, which is also associated with the WS protein.3 Therefore, central nerves undergoing fewer cell divisions may be associated with a small number of disorders. In conclusion, the frequency of stroke was lower in WS despite these individuals having numerous risk factors. A mutation in the WNR gene has been suggested as a possible protective process against the development of stroke. This finding may be significant for understanding the mechanism of the pathogenesis and progression of stroke, as well as for developing new therapeutic methods. This work was supported by Health and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare of Japan for the Research on Measures for Intractable Diseases. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Emiko Okabe: analysis and interpretation of data, preparation of manuscript. Minoru Takemoto: study concept and design, analysis and interpretation of data, preparation of manuscript, acquisition of subjects and data. Shunichiro Onishi, Takahiro Ishikawa, Ryouichi Ishibashi, Peng He, Kazuki Kobayashi, Masaki Fujimoto, and Harukiyo Kawamura: acquisition of subjects and data. Koutaro Yokote: study concept and design; preparation of manuscript. Sponsor's Role: None." @default.
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• W1978392275 date "2012-05-01" @default.
• W1978392275 modified "2023-10-17" @default.
• W1978392275 title "Incidence and Characteristics of Metabolic Disorders and Vascular Complications in Individuals with Werner Syndrome in Japan" @default.
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• W1978392275 doi "https://doi.org/10.1111/j.1532-5415.2012.03944.x" @default.
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