Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study.
OBJECTIVE
Brain-muscle-Arnt-like protein-1 (BMAL1) and BMAL2 genes are essential components of the circadian clock, and are considered to be involved in glucose homeostasis. We examined whether single nucleotide polymorphisms (SNPs) of BMAL1 and BMAL2 were associated with the prevalence of type 2 diabetes (T2DM) in the general Japanese population.


METHODS
We studied 2467 subjects (1232 men and 1235 women, 35-69 years old), including 105 men and 57 women with T2DM, from the participants of the Japan Multi-institutional Collaborative Cohort Study. The association between SNPs in the BMAL1 (rs11022775 and rs2290035) and BMAL2 (rs7958822) genes and T2DM were analyzed by multiple logistic regression after adjustment for potential confounders. Analysis was also performed after stratification by body mass index (≥25 kg/m(2) and <25 kg/m(2)) to investigate an interaction between genotypes and obesity.


RESULTS
The A/G and A/A genotypes of BMAL2 rs7958822 showed significantly higher adjusted odds ratios (OR) for T2DM than the G/G genotype among obese men (OR=2.2, 95% confidence intervals [CI] 1.1, 4.6, P for interaction=0.0495) and obese women (OR=2.7, 95% CI 1.1, 6.7, P for interaction=0.199). There were no significant associations between BMAL1 rs11022775 or rs2290035 genotypes and T2DM.


CONCLUSIONS
To the best of our knowledge, this is the first study to show the significant association between BMAL2 rs7958822 genotype and T2DM among obese subjects.
Department of Preventive Medicine, The Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan.
Miwa
M
Yamaguchi
Department of Preventive Medicine, The Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan.
Hirokazu
H
Uemura
Department of Preventive Medicine, The Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan. Electronic address: karisawa@tokushima-u.ac.jp.
Kokichi
K
Arisawa
Department of Preventive Medicine, The Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan.
Sakurako
S
Katsuura-Kamano
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya City, Aichi 466-8550, Japan.
Nobuyuki
N
Hamajima
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya City, Aichi 466-8550, Japan.
Asahi
A
Hishida
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya City, Aichi 466-8550, Japan; Department of Oral Disease Research, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu City, Aichi 474-8511, Japan.
Shino
S
Suma
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya City, Aichi 464-8681, Japan.
Isao
I
Oze
St Mary's College Faculty of Nursing, Tsubukuhonmachi 422, Kurume City, Fukuoka 830-8558, Japan.
Kazuyo
K
Nakamura
Department of Public Health, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192, Japan.
Naoyuki
N
Takashima
Department of Public Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya City, Aichi 467-8601, Japan.
Sadao
S
Suzuki
Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima 890-8544, Japan.
Rie
R
Ibusuki
Chiba Cancer Center Research Institute, Cancer Prevention Center, 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717, Japan.
Haruo
H
Mikami
Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-8582, Japan.
Keizo
K
Ohnaka
Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto City, Kyoto 602-8566, Japan.
Nagato
N
Kuriyama
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
Michiaki
M
Kubo
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya City, Aichi 464-8681, Japan.
Hideo
H
Tanaka
D056930:ARNTL Transcription Factors / Q000235:genetics*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; C486615:BMAL2 protein, human
Brain-muscle-Arnt-like protein; Gene–environment interaction; Obesity; Single nucleotide polymorphisms; Type 2 diabetes