Metabolism of oral antidiabetic: evaluation of CYP2C9 polymorphisms in Maya population

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 796-817-Diabetes Genetics & Epidemiology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-804
Marta Menjivar*1, Luz Camacho1, Julio Lara-Riegos1, Isela Montúfar-Robles2, María de los Angeles Granados-Silvestre1, Adrian Llerena3 and María Guadalupe Ortiz-López2
1Universidad Nacional Autónoma de México, México, DF, Mexico, 2Hospital Juárez de México, México, DF, Mexico, 3Extremadura University Hospital and Medical School, Badajoz, Spain
Introduction: Type 2 diabetes (DM2) is a chronic disease that represents a world-wide health and economic problem that in Mexico pertains to 14.4% of the total population1. Increasing successful treatments with reduced costs becomes imperative. Most commonly prescribed oral drugs for DM2 treatment, in México, are sulfonylureas. Diverse polymorphisms and mutations on CYP2C9 may modify the response to this kind of drugs, yielding enzymes with altered activity and as a consequence, circulating drug levels above or below the expected concentration, increasing the risk of adverse drug reactions or decreasing their efficacy2. One of the benefits of pharmacogenetics is to aid to optimize recommended drug dosages. However, to date only a few studies in this regard were done on Native Americans and no study has been carried out in Mayan population, which is one of the largest indigenous groups in Mexico (more than 7 millions). The aim of this work was thus, to identify the presence and frequency of the CYP2C9 variants *2 and *3 in Mayan population. Methods: 178 Mayan individual from all the states comprising the Yucatán peninsula were recruited for the study. Blood samples were collected to obtain DNA. Subjects met the following inclusion criteria: lifestyle, language, Maya ancestry (3 generations at least). Genotyping for CYP2C9*2 and *3 allelic variants was performed using fluorescence-based allele- specific TaqMan allelic discrimination assay. Project approved by Ethics committee of Hospital Juárez de México and consent agreement obtained. Results: The allele frequency of CYP2C9 *2 was 1.7 %, and 4.3 % for CYP2C9 *3. No homozygous for *2 or *3 variants were found. All results were in Hardy-Weinberg equilibrium. Conclusion: The frequencies detected in CYP2C9 polymorphisms in the Maya population studied were lower than those described for Mexican mestizos or Caucasian3. These data preclude no adverse effect upon the metabolism of sulfonylureas although, the negative impact on other drugs metabolism can not be ruled out. Furthermore, additional pharmacokinetic and pharmacodynamic tests must be performed in order to obtain a complete picture of drug metabolism in Maya population. Finally, the inclusion of all ethnic communities in clinical pharmacogenetic research studies could contribute to a better healthcare service to mestizo populations in Mexico.

Nothing to Disclose: MM, LC, JL, IM, MDLAG, AL, MGO

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