Abstract
Type 2 diabetes mellitus (T2DM) is one of the major public health problems worldwide; both genetic and environmental factors are its risk factors. Arsenic, an environmental pollutant, might be a risk factor for T2DM, but the association of low-to-moderate level arsenic exposure with the risk of T2DM is still inconsistent. Single nucleotide polymorphisms (SNPs) can affect the development of T2DM, but the study on KEAP1 rs11545829 (G>A) SNP is few. In this paper, we explored the effect of KEAP1 rs11545829 (G>A) SNP and low-to-moderate level arsenic exposure on risk of T2DM in a cross-sectional case–control study conducted in Shanxi, China. Total of 938 participants, including 318 T2DM cases and 618 controls, were enrolled. Blood glycosylated haemoglobin (HbA1c) was detected by Automatic Biochemical Analyzer, and participants with HbA1c≧6.5% were diagnosed as T2DM. Urinary total arsenic (tAs, mg/L), as the indicator of arsenic exposure, was detected by liquid chromatography–atomic fluorescence spectrometry (LC–AFS). Genomic DNA was extracted and the genotypes of KEAP1 rs11545829 SNP were examined by multiplex polymerase chain reaction (PCR). The urinary tAs concentration in recruited participants was 0.075 (0.03–0.15) mg/L, and was associated with an increased risk of T2DM (OR = 8.45, 95% CI 2.63–27.17); rs11545829 mutation homozygote AA genotype had a protective effect on risk of T2DM (OR = 0.42, 95 % CI 0.25–0.73). Although this protective effect of AA genotype was found in participants with higher urinary tAs level (>0.032 mg/L) (OR = 0.48, 95% CI 0.26–0.86), there was no interaction effect for arsenic exposure and rs11545829 SNP on risk of T2DM. In addition, BMI modified the association between rs11545829 SNP and the risk of T2DM (RERI = −1.11, 95% CI −2.18–0.04). The present study suggest that low-to-moderate level arsenic exposure may be a risk factor, while KEAP1 rs11545829 SNP mutation homozygote AA genotype may be a protective factor for risk of T2DM, especially for T2DM patients with urinary tAs level>0.032 mg/L.
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We sincerely thank all study participants, research staffs who participated in this work.
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This work was supported by the Key projects of National Natural Science Foundation of China (81830099).
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CF: conceptualization, methodology, visualization, and writing-original draft. ZZ: formal analysis and resources. XZ: formal analysis and resources. QL: investigation. N Gi: investigation. MS: resources. YG: resources. LW: formal analysis, resources, and investigation. WH: resources and investigation. MZ: resources and investigation. FY: investigation. YW: validation. JP: project administration and funding acquisition. YX: validation. YY: conceptualization, methodology, writing-review and editing, and supervision. YG: conceptualization, methodology, writing-review and editing, supervision, and project administration.
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Fan, C., Zhan, Z., Zhang, X. et al. Research for type 2 diabetes mellitus in endemic arsenism areas in central China: role of low level of arsenic exposure and KEAP1 rs11545829 polymorphism. Arch Toxicol 96, 1673–1683 (2022). https://doi.org/10.1007/s00204-022-03279-1
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DOI: https://doi.org/10.1007/s00204-022-03279-1