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Genetic susceptibility to pre diabetes mellitus and related association with obesity and physical fitness components in Mexican-Mestizos

  • Paula Costa-Urrutia
    Correspondence
    Corresponding author at: Department of Cell and Developmental Biology Institute of Biomedical Sciences, Faculty of Medicine, University of São Paulo, Av. Prof. Lineu Prestes, 2415, São Paulo, Brazil.
    Affiliations
    Department of Cell and Developmental Biology Institute of Biomedical Sciences, Faculty of Medicine, University of São Paulo, Av. Prof. Lineu Prestes, 2415, São Paulo, Brazil

    Sport City, SA de CV, Grupo Marti, Blvd Adolfo López Mateos 1181, San Pedro de los Pinos, ZC: 01180 Álvaro Obregón, Mexico City, Mexico
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  • Carolina Abud
    Affiliations
    Sport City, SA de CV, Grupo Marti, Blvd Adolfo López Mateos 1181, San Pedro de los Pinos, ZC: 01180 Álvaro Obregón, Mexico City, Mexico
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  • Valentina Franco-Trecu
    Affiliations
    Departamento de Ecología y Evolución, Facultad de Ciencias, Universidad de la República, Iguá 4225, ZC: 11400 Montevideo, Uruguay
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  • Valentina Colistro
    Affiliations
    Departamento de Genética, Facultad de Medicina, Universidad de la República, Av. Gral. Flores 2125, ZC: 11800 Montevideo, Uruguay
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  • Martha Eunice Rodríguez-Arellano
    Affiliations
    Laboratorio de Medicina Genómica del Hospital Regional Lic, Adolfo López Mateos, ISSSTE, Av. Universidad 1321, Florida, ZC: 01030 Álvaro Obregón, Mexico City, Mexico
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  • Julio Granados
    Affiliations
    División de Inmunogenética, Departamento de Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, ZC: 14080, Mexico City, Mexico
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  • Marilia Seelaender
    Affiliations
    Department of Cell and Developmental Biology Institute of Biomedical Sciences, Faculty of Medicine, University of São Paulo, Av. Prof. Lineu Prestes, 2415, São Paulo, Brazil
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      Highlights

      • Pre diabetes mellitus (pre-DM) was associated to ASCL1 rs9997745 and PPARGC1A rs8192678 mutations.
      • The effect of ASCL1 rs9997745 on pre-DM was modulated by obesity.
      • PPARGC1A rs8192678 was associated to pre-DM risk in subjects with obesity.
      • For PPARGC1A rs8192678 the effect was attenuated by higher cardiorespiratory values.
      • Genetic assessment may help preventing pre-DM from progressing to type two diabetes.

      Abstract

      Pre diabetes mellitus (pre-DM) is considered an early-reversible condition that can progress to Type 2 diabetes mellitus (T2DM) which is the main cause of death for adult Mexican population. Gene variants influencing fasting glucose levels may constitute helpful tool for prevention purposes in pre-DM condition. Physically active Mexican-Mestizo adults (n = 565) were genotyped for 6 single nucleotide polymorphisms (SNPs) (ADIPOQ rs2241766, ACSL1 rs9997745, LIPC rs1800588, PPARA rs1800206, PPARG rs1801282 and PPARGC1A rs8192678) related to lipid and carbohydrate metabolism. Fasting glucose was measured and values classified as pre-DM (≥100 mg/dL) or normal fasting glucose. Logistic models were used to test associations between pre-DM condition and SNPs, and interaction with Body Mass Index (BMI) and physical fitness components. The A allele of ASCL1 rs9997745 conferred increased risk (OR = 3.39, p = 0.001) of pre-DM which is modulated by BMI. The A allele of the PPARGC1A rs8192678 showed significant SNP*BMI (OR = 1.10, p = 0.008) interaction effect for pre-DM risk, meaning that obese subjects showed higher pre-DM risk but normal weight subjects showed lower risk. The effect increased with age and was attenuated by higher cardiorespiratory values. We found that both ACSL1 rs9997745 and PPARGC1A rs8192678 are associated with pre-DM, and that BMI significantly modified their association.

      Keywords

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