Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies.
Metallothioneins (MTs) are proteins that protect cells from toxic agents such as heavy metal ions or reactive oxygen species. MT2A A-5G is a single nucleotide polymorphism in the promoter region of the MT2A gene, and the minor G allele results in lower transcription efficiency. We aimed to elucidate associations between MT2A A-5G and risks of 2 diseases potentially related to lowered MT expression, chronic kidney disease (CKD), and diabetes mellitus (DM), in a community-dwelling population. Study subjects were Nagoya city residents participating in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC) Daiko Study, comprised 749 men and 2,025 women, aged 39-75 years. CKD (>stage 3) and DM were defined by standard guidelines. Associations were evaluated using logistic regression models with adjustments for age, sex and potential confounders in a cross-sectional study, and verified in a 5-year longitudinal study. Odds ratios (OR [95% confidence interval]) were calculated relative to the AA genotype. Serum MT (I + II), Cd and zinc levels were also determined by genotype. The OR of the GG genotype for CKD risk was 3.98 (1.50, 10.58) in the cross-sectional study and 5.17 (1.39, 19.28) in the longitudinal study. The OR of the GA genotype for DM was 1.86 (1.26, 2.75) in the cross-sectional study and 2.03 (1.19, 3.46) in the longitudinal study. MT2A A-5G may be associated with CKD and DM risks. This polymorphism is a promising target for evaluations of CKD and DM risks with possible involvement of low-dose chronic exposure to environmental pollutants.
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan u-ta.h@med.nagoya-u.ac.jp.
Yuta
Y
Hattori
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Mariko
M
Naito
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, 464-8650, Japan.
Masahiko
M
Satoh
Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, 466-8550, Japan.
Masahiro
M
Nakatochi
Department of Public Health, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.
Hisao
H
Naito
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Masashi
M
Kato
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Sahoko
S
Takagi
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Takashi
T
Matsunaga
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Toshio
T
Seiki
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Tae
T
Sasakabe
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan;
Shino
S
Suma
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Sayo
S
Kawai
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Rieko
R
Okada
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Asahi
A
Hishida
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Nobuyuki
N
Hamajima
*Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Kenji
K
Wakai
D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008668:Metallothionein / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors; D015032:Zinc / Q000097:blood
C491053:MT2A protein, human; D008668:Metallothionein; D015032:Zinc
SNP; chronic kidney disease; diabetes mellitus; metallothionein; risk assessment