Metallothionein MT2A A-5G polymorphism as a risk factor for chronic kidney disease and diabetes

Cross-sectional and cohort studies

Yuta Hattori, Mariko Naito, Masahiko Satoh, Masahiro Nakatochi, Hisao Naito, Masashi Kato, Sahoko Takagi, Takashi Matsunaga, Toshio Seiki, Tae Sasakabe, Shino Suma, Sayo Kawai, Rieko Okada, Asahi Hishida, Nobuyuki Hamajima, Kenji Wakai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-193
Number of pages13
JournalToxicological Sciences
Volume152
Issue number1
DOIs
Publication statusPublished - 01-07-2016

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Metallothionein
Medical problems
Polymorphism
Chronic Renal Insufficiency
Diabetes Mellitus
Cohort Studies
Cross-Sectional Studies
Genotype
Longitudinal Studies
Logistic Models
Independent Living
Heavy Ions
Environmental Pollutants
Poisons
Heavy Metals
Genetic Promoter Regions
Single Nucleotide Polymorphism
Transcription
Zinc
Reactive Oxygen Species

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Hattori, Yuta ; Naito, Mariko ; Satoh, Masahiko ; Nakatochi, Masahiro ; Naito, Hisao ; Kato, Masashi ; Takagi, Sahoko ; Matsunaga, Takashi ; Seiki, Toshio ; Sasakabe, Tae ; Suma, Shino ; Kawai, Sayo ; Okada, Rieko ; Hishida, Asahi ; Hamajima, Nobuyuki ; Wakai, Kenji. / Metallothionein MT2A A-5G polymorphism as a risk factor for chronic kidney disease and diabetes : Cross-sectional and cohort studies. In: Toxicological Sciences. 2016 ; Vol. 152, No. 1. pp. 181-193.
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abstract = "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.",
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Hattori, Y, Naito, M, Satoh, M, Nakatochi, M, Naito, H, Kato, M, Takagi, S, Matsunaga, T, Seiki, T, Sasakabe, T, Suma, S, Kawai, S, Okada, R, Hishida, A, Hamajima, N & Wakai, K 2016, 'Metallothionein MT2A A-5G polymorphism as a risk factor for chronic kidney disease and diabetes: Cross-sectional and cohort studies', Toxicological Sciences, vol. 152, no. 1, pp. 181-193. https://doi.org/10.1093/toxsci/kfw080

Metallothionein MT2A A-5G polymorphism as a risk factor for chronic kidney disease and diabetes : Cross-sectional and cohort studies. / Hattori, Yuta; Naito, Mariko; Satoh, Masahiko; Nakatochi, Masahiro; Naito, Hisao; Kato, Masashi; Takagi, Sahoko; Matsunaga, Takashi; Seiki, Toshio; Sasakabe, Tae; Suma, Shino; Kawai, Sayo; Okada, Rieko; Hishida, Asahi; Hamajima, Nobuyuki; Wakai, Kenji.

In: Toxicological Sciences, Vol. 152, No. 1, 01.07.2016, p. 181-193.

Research output: Contribution to journalArticle

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AU - Hattori, Yuta

AU - Naito, Mariko

AU - Satoh, Masahiko

AU - Nakatochi, Masahiro

AU - Naito, Hisao

AU - Kato, Masashi

AU - Takagi, Sahoko

AU - Matsunaga, Takashi

AU - Seiki, Toshio

AU - Sasakabe, Tae

AU - Suma, Shino

AU - Kawai, Sayo

AU - Okada, Rieko

AU - Hishida, Asahi

AU - Hamajima, Nobuyuki

AU - Wakai, Kenji

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

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