CVClient

Hirokazu Uemura

  (上村 浩一)

Profile Information

Affiliation
Professor, Department of Health and Welfare System, College of Nursing Art and Science, University of Hyogo
Degree
-(The University of Tokushima)

Contact information
hirokazu_uemuracnas.u-hyogo.ac.jp
J-GLOBAL ID
200901016860174067
researchmap Member ID
5000019925

社会医学系指導医・専門医、日本疫学会認定上級疫学専門家、日本公衆衛生学会認定専門家、日本医師会認定産業医、衛生学エキスパート、産婦人科専門医、日本女性医学学会認定女性ヘルスケア専門医、日本産婦人科乳腺医学会乳房疾患認定医

日本公衆衛生学会(代議員)、日本女性医学学会(代議員、査読委員)、日本産婦人科乳腺医学会(副幹事長、代議員)、日本産科婦人科学会・女性ヘルスケア委員会小委員会委員

西宮市環境影響評価専門委員会委員、NPO法人徳島乳がんネットワーク委員、徳島市健康づくり推進協議会委員(会長)(~令和2年3月)、粉じん対策指導委員(徳島労働局)(~令和2年3月)、徳島県立保健製薬環境センター試験研究評価委員会委員)(~令和2年3月)、公益財団法人徳島県総合健診センター・倫理審査委員会委員)(~令和2年3月)、NPO法人AWAがん対策募金・がん検診率向上プロジェクト委員)(~令和2年3月)


Major Papers

 221
  • Kenji Takeuchi, Mariko Naito, Sayo Kawai, Mineko Tsukamoto, Yuka Kadomatsu, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Masahiro Nakatochi, Tae Sasakabe, Shuji Hashimoto, Hidetaka Eguchi, Yukihide Momozawa, Hiroaki Ikezaki, Masayuki Murata, Norihiro Furusyo, Keitaro Tanaka, Megumi Hara, Yuichiro Nishida, Keitaro Matsuo, Hidemi Ito, Isao Oze, Haruo Mikami, Yohko Nakamura, Miho Kusakabe, Toshiro Takezaki, Rie Ibusuki, Ippei Shimoshikiryo, Sadao Suzuki, Takeshi Nishiyama, Miki Watanabe, Teruhide Koyama, Etsuko Ozaki, Isao Watanabe, Kiyonori Kuriki, Yoshikuni Kita, Hirotsugu Ueshima, Kenji Matsui, Kokichi Arisawa, Hirokazu Uemura, Sakurako Katsuura-Kamano, Sho Nakamura, Hiroto Narimatsu, Nobuyuki Hamajima, Hideo Tanaka, Kenji Wakai
    Journal of Epidemiology, 31(12) 660-668, Sep, 2020  Peer-reviewed
    BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.
  • Kazuyoshi Ishigaki, Masato Akiyama, Masahiro Kanai, Atsushi Takahashi, Eiryo Kawakami, Hiroki Sugishita, Saori Sakaue, Nana Matoba, Siew-Kee Low, Yukinori Okada, Chikashi Terao, Tiffany Amariuta, Steven Gazal, Yuta Kochi, Momoko Horikoshi, Ken Suzuki, Kaoru Ito, Satoshi Koyama, Kouichi Ozaki, Shumpei Niida, Yasushi Sakata, Yasuhiko Sakata, Takashi Kohno, Kouya Shiraishi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Masashi Ikeda, Nakao Iwata, Shiro Ikegawa, Ikuyo Kou, Toshihiro Tanaka, Hidewaki Nakagawa, Akari Suzuki, Tomomitsu Hirota, Mayumi Tamari, Kazuaki Chayama, Daiki Miki, Masaki Mori, Satoshi Nagayama, Yataro Daigo, Yoshio Miki, Toyomasa Katagiri, Osamu Ogawa, Wataru Obara, Hidemi Ito, Teruhiko Yoshida, Issei Imoto, Takashi Takahashi, Chizu Tanikawa, Takao Suzuki, Nobuaki Sinozaki, Shiro Minami, Hiroki Yamaguchi, Satoshi Asai, Yasuo Takahashi, Ken Yamaji, Kazuhisa Takahashi, Tomoaki Fujioka, Ryo Takata, Hideki Yanai, Akihide Masumoto, Yukihiro Koretsune, Hiromu Kutsumi, Masahiko Higashiyama, Shigeo Murayama, Naoko Minegishi, Kichiya Suzuki, Kozo Tanno, Atsushi Shimizu, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Hirokazu Uemura, Keitaro Tanaka, Mariko Naito, Makoto Sasaki, Kenji Wakai, Shoichiro Tsugane, Masayuki Yamamoto, Kazuhiko Yamamoto, Yoshinori Murakami, Yusuke Nakamura, Soumya Raychaudhuri, Johji Inazawa, Toshimasa Yamauchi, Takashi Kadowaki, Michiaki Kubo, Yoichiro Kamatani
    Nature genetics, 52(7) 669-679, Jul, 2020  Peer-reviewed
    The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10-9). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.
  • Yusuke Kawamura, Hirofumi Nakaoka, Akiyoshi Nakayama, Yukinori Okada, Ken Yamamoto, Toshihide Higashino, Masayuki Sakiyama, Toru Shimizu, Hiroshi Ooyama, Keiko Ooyama, Mitsuo Nagase, Yuji Hidaka, Yuko Shirahama, Kazuyoshi Hosomichi, Yuichiro Nishida, Ippei Shimoshikiryo, Asahi Hishida, Sakurako Katsuura-Kamano, Seiko Shimizu, Makoto Kawaguchi, Hirokazu Uemura, Rie Ibusuki, Megumi Hara, Mariko Naito, Mikiya Takao, Mayuko Nakajima, Satoko Iwasawa, Hiroshi Nakashima, Keizo Ohnaka, Takahiro Nakamura, Blanka Stiburkova, Tony R Merriman, Masahiro Nakatochi, Sahoko Ichihara, Mitsuhiro Yokota, Tappei Takada, Tatsuya Saitoh, Yoichiro Kamatani, Atsushi Takahashi, Kokichi Arisawa, Toshiro Takezaki, Keitaro Tanaka, Kenji Wakai, Michiaki Kubo, Tatsuo Hosoya, Kimiyoshi Ichida, Ituro Inoue, Nariyoshi Shinomiya, Hirotaka Matsuo
    Annals of the rheumatic diseases, 78(10) 1430-1437, Oct, 2019  Peer-reviewed
    OBJECTIVE: The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. METHODS: We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). RESULTS: This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10-8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three 'gout vs AHUA GWAS'-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. CONCLUSIONS: This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.
  • Masahiro Nakatochi, Masahiro Kanai, Akiyoshi Nakayama, Asahi Hishida, Yusuke Kawamura, Sahoko Ichihara, Masato Akiyama, Hiroaki Ikezaki, Norihiro Furusyo, Seiko Shimizu, Ken Yamamoto, Makoto Hirata, Rieko Okada, Sayo Kawai, Makoto Kawaguchi, Yuichiro Nishida, Chisato Shimanoe, Rie Ibusuki, Toshiro Takezaki, Mayuko Nakajima, Mikiya Takao, Etsuko Ozaki, Daisuke Matsui, Takeshi Nishiyama, Sadao Suzuki, Naoyuki Takashima, Yoshikuni Kita, Kaori Endoh, Kiyonori Kuriki, Hirokazu Uemura, Kokichi Arisawa, Isao Oze, Keitaro Matsuo, Yohko Nakamura, Haruo Mikami, Takashi Tamura, Hiroshi Nakashima, Takahiro Nakamura, Norihiro Kato, Koichi Matsuda, Yoshinori Murakami, Tatsuaki Matsubara, Mariko Naito, Michiaki Kubo, Yoichiro Kamatani, Nariyoshi Shinomiya, Mitsuhiro Yokota, Kenji Wakai, Yukinori Okada, Hirotaka Matsuo
    Communications Biology, 2(1), Apr 8, 2019  Peer-reviewed
    , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.
  • Uemura H, Katsuura-Kamano S, Iwasaki Y, Arisawa K, Hishida A, Okada R, Tamura T, Kubo Y, Ito H, Oze I, Shimanoe C, Nishida Y, Nakamura Y, Takashima N, Suzuki S, Nakagawa-Senda H, Nishimoto D, Takezaki T, Mikami H, Nakamura Y, Furusyo N, Ikezaki H, Ozaki E, Koyama T, Kuriki K, Endoh K, Naito M, Wakai K, Japan Multi-institutional Collaborative Cohort, J-MICC, Study Group
    Endocrine, 64(3) 552-563, Apr, 2019  Peer-reviewed
    PURPOSE: This study aimed to investigate independent relationships of daily non-exercise life activity and leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits in Japanese adults. METHODS: Data of 24,625 eligible subjects (12,709 men, 11,916 women) who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were analyzed. Information about lifestyle characteristics was obtained from a questionnaire. Logistic regression analyses were performed to evaluate the independent associations of daily life activity as well as leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits by sex. RESULTS: Male subjects with higher daily life activity as well as with higher leisure-time exercise volume had a lower prevalence of metabolic syndrome, independently with each other. Female subjects with higher daily life activity also had a lower prevalence of metabolic syndrome. Particularly, male and female subjects with the highest daily life activity quartile showed considerably low odds ratios of 0.66 (95% CI, 0.53-0.81) and 0.64 (0.52-0.79), respectively, for low HDL-cholesterol even after the adjustment for BMI compared with the first quartile. Meanwhile, male subjects with the higher leisure-time exercise showed a quite lower prevalence of elevated triglycerides. Higher moderate-intensity exercise was more intensely associated with a lower prevalence of metabolic syndrome and some of its traits in both sexes. CONCLUSIONS: Our results suggest that higher daily life activity and higher moderate-intensity exercise may be independently associated with a lower risk of metabolic syndrome in Japanese adults.
  • Uemura H, Katsuura-Kamano S, Nakamoto M, Yamaguchi M, Fujioka M, Iwasaki Y, Arisawa K
    Scientific reports, 8(1) 9667-9667, Jun 25, 2018  Peer-reviewed
    Studies on the associations between soy food consumption and arterial stiffness are rare. The aim of the present study was to evaluate their associations in Japanese men. A total of 652 eligible men, aged 35-69 years, who underwent the measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated in this cross-sectional study. Information on their lifestyle characteristics, including dietary behavior, was obtained from a structured self-administered questionnaire. The frequency of total soy products as well as fermented and non-fermented soy products intakes was calculated, and the amounts of soy protein and soy isoflavone intakes were also estimated; these were then divided into tertiles and their associations with baPWV values were evaluated using general linear models. Higher frequency of fermented soy products intake was associated with decreased baPWV after adjusting for the multivariable covariates (P value for trend was 0.002, in Model 3). This association did not alter after further adjustment with a biomarker of systemic inflammation (serum high-sensitivity C-reactive protein (hs-CRP)) (P value for trend was 0.001, in Model 4). Total soy isoflavone consumption was also inversely associated with baPWV even after adjusting for multivariable covariates including serum hs-CRP (P value for trend was 0.043, in Model 4); however total soy protein consumption was not. These results demonstrated that greater consumption of soy food, especially fermented soy products and soy isoflavone was associated with reduced arterial stiffness, independent of systemic inflammation, in Japanese men.
  • Hirokazu Uemura, A. Ammar Ghaibeh, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Tirani Bahari, Masashi Ishizu, Hiroki Moriguchi, Kokichi Arisawa
    SCIENTIFIC REPORTS, 7 45502-45502, Mar, 2017  Peer-reviewed
    To investigate unknown patterns associated with type 2 diabetes in the Japanese population, we first used an alternating decision tree (ADTree) algorithm, a powerful classification algorithm from data mining, for the data from 1,102 subjects aged 35-69 years. On the basis of the investigated patterns, we then evaluated the associations of serum high-sensitivity C-reactive protein (hs-CRP) as a biomarker of systemic inflammation and family history of diabetes (negative, positive or unknown) with the prevalence of type 2 diabetes because their detailed associations have been scarcely reported. Elevated serum hs-CRP levels were proportionally associated with the increased prevalence of type 2 diabetes after adjusting for probable covariates, including body mass index and family history of diabetes (P for trend = 0.016). Stratified analyses revealed that elevated serum hs-CRP levels were proportionally associated with increased prevalence of diabetes in subjects without a family history of diabetes (P for trend = 0.020) but not in those with a family history or with an unknown family history of diabetes. Our study demonstrates that systemic inflammation was proportionally associated with increased prevalence of type 2 diabetes even after adjusting for body mass index, especially in subjects without a family history of diabetes.
  • Hirokazu Uemura, Sakurako Katsuura-Kamano, Miwa Yamaguchi, Kokichi Arisawa
    ATHEROSCLEROSIS, 238(1) 83-88, Jan, 2015  Peer-reviewed
    Objective: The present study aimed to evaluate the relationships between elevated serum levels of hepatic enzymes and arterial stiffness and to investigate whether alcohol intake had a modifying effect on these relationships in Japanese men. Methods: A total of 647 eligible men aged 35-69 years who underwent measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated. Information on their lifestyle characteristics were obtained from a structured self-administered questionnaire. Serum biochemical factors, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were determined. The serum ALT and GGT levels were divided into tertiles, and their associations with baPWV values were evaluated using general linear models adjusted for potential confounding factors. The interaction effects between serum hepatic enzymes and alcohol intake on baPWV were further evaluated. Results: Elevated serum ALT and GGT levels were proportionally associated with increased baPWV after adjusting for the multivariable covariates (P values for trend, 0.004 and 0.003, respectively). Further analyses revealed that the proportional associations between serum levels of hepatic enzymes and baPWV were striking in the subjects without alcohol intake but not in those with alcohol intake. The interaction effect between serum GGT level and alcohol intake on baPWV was significant (P for interaction, 0.042). Conclusion: These results demonstrate that elevated serum ALT and GGT levels are associated with increased arterial stiffness, independent of the classical atherosclerotic risk factors in Japanese men, and that the association of elevated serum GGT level with arterial stiffness differs according to alcohol intake. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
  • Uemura H
    Nihon eiseigaku zasshi. Japanese journal of hygiene, 67(3) 363-374, May, 2012  Peer-reviewed
    Persistent organic pollutants (POPs) are a group of chemical substances that have the common properties of resistance to biodegradation, wide-range transportation, high lipophilicity, bioaccumulation in fat, and biomagnification in the food chain. POPs are persistent in the environment worldwide and have potential adverse impacts on human health and the environment. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are well known chemicals that are considered as POPs.<br> The association between high-level exposure to dioxins and type 2 diabetes among U.S. Air Force veterans who had been exposed to Agent Orange contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the Vietnam War was reported in the late 1990s. This association has been supported by similar epidemiologic studies, whose subjects were exposed to high doses of dioxins in their places of work involving phenoxyacid herbicide production and spraying, and in the industrial accident in Seveso, Italy.<br> Recently, low-level exposure to dioxins and PCBs has been reported to be linked to type 2 diabetes. Cross-sectional studies in the U.S. general population and Japanese general population showed that body burden levels of some dioxins and PCBs were strongly associated with the prevalence of type 2 diabetes. Very recently, following these cross-sectional studies, several prospective studies have suggested that low-level exposure to some PCBs predicted the future risk of type 2 diabetes in the general population. Environmental exposure to some dioxins and PCBs, which mainly accumulate in adipose tissue, may play a role in the development of type 2 diabetes.<br>
  • Kenji Wakai, Nobuyuki Hamajima, Rieko Okada, Mariko Naito, Emi Morita, Asahi Hishida, Sayo Kawai, Kazuko Nishio, Guang Yin, Yatami Asai, Keitaro Matsuo, Satoyo Hosono, Hidemi Ito, Miki Watanabe, Takakazu Kawase, Takeshi Suzuki, Kazuo Tajima, Keitaro Tanaka, Yasuki Higaki, Megumi Hara, Takeshi Imaizumi, Naoto Taguchi, Kazuyo Nakamura, Hinako Nanri, Tatsuhiko Sakamoto, Mikako Horita, Koichi Shinchi, Yoshikuni Kita, Tanvir Chowdhury Turin, Nahid Rumana, Kenji Matsui, Katsuyuki Miura, Hirotsugu Ueshima, Naoyuki Takashima, Yasuyuki Nakamura, Sadao Suzuki, Ryosuke Ando, Akihiro Hosono, Nahomi Imaeda, Kiyoshi Shibata, Chiho Goto, Nami Hattori, Mitsuru Fukatsu, Tamaki Yamada, Shinkan Tokudome, Toshiro Takezaki, Hideshi Niimura, Kazuyo Hirasada, Akihiko Nakamura, Masaya Tatebo, Shin Ogawa, Noriko Tsunematsu, Shirabe Chiba, Haruo Mikami, Suminori Kono, Keizo Ohnaka, Ryoichi Takayanagi, Yoshiyuki Watanabe, Etsuko Ozaki, Masako Shigeta, Nagato Kuriyama, Aya Yoshikawa, Daisuke Matsui, Isao Watanabe, Kaoru Inoue, Kotaro Ozasa, Satoko Mitani, Kokichi Arisawa, Hirokazu Uemura, Mineyoshi Hiyoshi, Hidenobu Takami, Miwa Yamaguchi, Mariko Nakamoto, Hideo Takeda, Michiaki Kubo, Hideo Tanaka
    JOURNAL OF EPIDEMIOLOGY, 21(3) 223-235, May, 2011  Peer-reviewed
    Background: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. Methods: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. Results: The study group comprised 2124 men and 2395 women with a mean age of 55.8 +/- 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency &gt;= 0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P &lt; 0.001). Conclusions: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.
  • Hirokazu Uemura, Kokichi Arisawa, Mineyoshi Hiyoshi, Atsushi Kitayama, Hidenobu Takami, Fusakazu Sawachika, Satoru Dakeshita, Kentaro Nii, Hiroshi Satoh, Yoshio Sumiyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki, Masaki Nagai, Tsuguyoshi Suzuki
    ENVIRONMENTAL HEALTH PERSPECTIVES, 117(4) 568-573, Apr, 2009  Peer-reviewed
    BACKGROUND: Environmental exposure to some persistent organic pollutants has been reported to be associated with metabolic syndrome in the U.S. population. OBJECTIVES: We evaluated the associations of body burden levels of dioxins and related compounds with the prevalence of metabolic syndrome among the general population in Japan. METHODS: We conducted a cross-sectional study with 1,374 participants not occupationally exposed to these pollutants, living throughout Japan during 2002-2006. In fasting blood samples, we measured biochemical factors and determined lipid-adjusted concentrations of 10 polychlorinated dibenzo-p-dioxins (PCDDs), 7 polychlorinated dibenzofurans (PCDFs), and 12 dioxin-like polychlorinated biphenyls (DL-PCBs) all of which have toxic equivalency factors. We also performed a questionnaire survey. RESULTS: The toxic equivalents (TEQs) of PCDDs, PCDFs, and DL-PCBs and total TEQs had significant adjusted associations with metabolic syndrome, whether or not we excluded diabetic subjects. By analyzing each component of metabolic syndrome separately, the DL-PCB TEQs and total TEQs were associated with all components, and the odds ratios (ORs) in the highest quartile of DL-PCB TEQs in four of the five components were higher than those for PCDDs or PCDFs. We also found congener-specific associations with metabolic syndrome; in particular, the highest quartiles of PCB-126 and PCB-105 had adjusted ORs of 9.1 and 7.3, respectively. compounds. CONCLUSIONS: These results suggest that body burden levels of dioxins and related particularly those of DL-PCBs, are associated with metabolic syndrome. Of the components, high blood pressure, elevated triglycerides, and glucose intolerance were most closely associated with these pollutants.
  • Hirokazu Uemura, Kokichi Arisawa, Mineyoshi Hiyoshi, Hiroshi Satoh, Yoshio Surniyoshi, Kenji Morinaga, Kazunori Kodama, Taka-ichiro Suzuki, Masaki Nagai, Tsuguyoshi Suzuki
    ENVIRONMENTAL RESEARCH, 108(1) 63-68, Sep, 2008  Peer-reviewed
    The aim of this study was to evaluate the associations of environmental exposure to dioxins with diabetes among general inhabitants in Japan. A cross-sectional study was performed on 1374 participants, who were not occupationally exposed to dioxins, aged 15-73 years, living widely in 75 different residential areas of 25 prefectures in Japan through 2002-2006. Seven polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), 12 dioxin-like polychlorinated biphenyls (PCBs), which are assigned a toxic equivalency factor, and biochemical factors were determined in fasting blood. A questionnaire survey on life-style including past history of diseases and treatments was also performed. We examined the associations of the accumulated toxic equivalents (TEQs) of PCDDs+PCDFs, dioxin-like PCBs and total dioxins with prevalent diabetes. Simple and partial correlation analyses revealed that HbA1c correlated with the accumulated TEQs of PCDDs+PCDFs, dioxin-like PCBs and total dioxins. In logistic regression analyses, the third and the highest quartiles of dioxin-like PCBs had adjusted odds ratios (ORs) of 3.07 (95% CI 1.16-8.81) and 6.82 (95% CI 2.59-20.1) compared to the reference (first plus second quartiles). On the other hand, the highest but not the third quartiles of PCDDs+PCDFs and total dioxins had significantly higher adjusted ORs compared to the respective references. These associations persisted when the subjects with poor liver or poor renal function were removed from the analysis. This recent representative data from general inhabitants in Japan showed associations of environmental exposure to dioxins, especially dioxin-like PCBs, with diabetes. (C) 2008 Elsevier Inc. All rights reserved.
  • H Uemura, T Yasui, M Kiyokawa, A Kuwahara, H Ikawa, T Matsuzaki, M Maegawa, H Furumoto, M Irahara
    JOURNAL OF ENDOCRINOLOGY, 174(2) 353-359, Aug, 2002  Peer-reviewed
    Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P&lt;0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P&lt;0.01 and P&lt;0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P&lt;0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P&lt;0.01) increased immediately before delivery to 1.40 +/- 0.53 ng/ml (means +/- S.D.) compared with those in the non-pregnant, non-lactating controls (0.58 +/- 0.11 ng/ml). After delivery, they fell rapidly to 0.87 +/- 0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.
  • H Uemura, M Irahara, N Yoneda, T Yasui, K Genjida, KI Miyamoto, T Aono, E Takeda
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 85(3) 1215-1219, Mar, 2000  
    To determine the influence of estrogen on the activity of renal proximal tubular reabsorption of inorganic phosphate (Pi) in women, we examined the changes of the renal threshold phosphate concentration (also denoted as TmP/GFR), as well as the changes in the concentrations of mineral components in the circulation in two groups of women-one receiving hormone replacement therapy (HRT) and one receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We also examined the changes in the concentrations of serum PTH in the GnRH-a group. The patients in the HRT group were continuously treated with 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate per day. The patients in the GnRH-a group were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. The values of TmP/GFR decreased in all of the patients who received HRT. The mean percentage change in TmP/GFR was -14.5% (range, -24.3% to -9.6%). In contrast, in all of the patients treated with GnRH-a, the values of TmP/GFR increased after 6 months of treatment (the mean percentage change was 28.5%; range, 18.2-78.3%) and returned to the preadministration level at 12 weeks after stopping therapy. In these patients, both the values of TmP/GFR and the concentrations of serum Pi correlated significantly with circulating estradiol levels (r = -0.767, P &lt; 0.01 and r = -0.797, P &lt; 0.01, respectively), but the concentrations of serum corrected calcium did not correlate. Moreover, in the same patients, the levels of serum intact PTH decreased significantly (P &lt; 0.05) after 6 months of treatment, but at 12 weeks after stopping therapy the trends of these levels varied among individual patients. These results suggest that estrogen could act directly to suppress sodium-dependent Pi reabsorption in the renal proximal tubules.

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