América L Miranda-Lora1, Mario Molina-Díaz2, Miguel Cruz3, Rocío Sánchez-Urbina4, Nancy L Martínez-Rodríguez5, Briceida López-Martínez6, Miguel Klünder-Klünder7,8. 1. Research Unit of Medicine Based on Evidence, Mexico Children's Hospital Federico Gómez, Mexico City, Mexico. 2. Department of Endocrinology, Mexico Children's Hospital Federico Gómez, Mexico City, Mexico. 3. Medical Research Unit in Biochemistry, Hospital de Especialidades Centro Médico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico. 4. Research Laboratory in Developmental Biology and Experimental Teratogenesis, Mexico Children's Hospital Federico Gómez, Mexico City, Mexico. 5. Departament of Community Health Research, Mexico Children's Hospital Federico Gómez, Mexico City, Mexico. 6. Deputy Director of Auxiliary Diagnostic Services, Mexico Children's Hospital Federico Gómez, Mexico City, Mexico. 7. Deputy Director of Research, Mexico Children's Hospital Federico Gómez, Mexico City, Mexico. 8. Research Committee, Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN), Mexico City, Mexico.
Abstract
BACKGROUND AND OBJECTIVE: Genetics play a very strong role in the development of pediatric-onset type 2 diabetes (T2D); however, little information exists about specific common single nucleotide polymorphisms (SNPs) associated with T2D in this age group. The aim of the study was to analyze the association and parental transmission of 64 obesity-related SNPs with pediatric-onset T2D in Mexican families. METHODS: A total of 57 pedigrees containing 171 probands with pediatric-onset T2D and 119 unrelated controls older than 18 years were included. The participants were genotyped for 64 polymorphisms. Association of each variant with pediatric-onset T2D was analyzed through a parent-offspring transmission disequilibrium test (TDT) and in a case-control comparison by χ2 analysis. RESULTS: Five SNPs exhibited associations with pediatric-onset T2D in the combined case-parent trio and case-control analysis: LINGO/rs10968576 (odds ratio [OR] 1.82, P = 0.003), POC5/rs2112347 (OR 1.96, P = 2.4E-5), RPS10-NUDT3/rs206936 (OR 1.40, P = 0.023), GLIS3/rs7034200 (OR 2.34, P = 1.2E-6), and VEGFA/rs6905288 (OR 1.58, P = 0.015). The first three were also associated with obesity status. The SNPs POC5/rs2112347 and RPS10-NUDT3/rs206936 were significantly associated through the maternal allele and GLIS3/rs7034200 through the paternal allele (P < 0.05). CONCLUSIONS: These findings suggest that certain SNPs associated with obesity and other metabolic traits may also be involved in risk of pediatric-onset T2D in Mexican families. We also identified preferential transmission of parental alleles in some variants.
BACKGROUND AND OBJECTIVE: Genetics play a very strong role in the development of pediatric-onset type 2 diabetes (T2D); however, little information exists about specific common single nucleotide polymorphisms (SNPs) associated with T2D in this age group. The aim of the study was to analyze the association and parental transmission of 64 obesity-related SNPs with pediatric-onset T2D in Mexican families. METHODS: A total of 57 pedigrees containing 171 probands with pediatric-onset T2D and 119 unrelated controls older than 18 years were included. The participants were genotyped for 64 polymorphisms. Association of each variant with pediatric-onset T2D was analyzed through a parent-offspring transmission disequilibrium test (TDT) and in a case-control comparison by χ2 analysis. RESULTS: Five SNPs exhibited associations with pediatric-onset T2D in the combined case-parent trio and case-control analysis: LINGO/rs10968576 (odds ratio [OR] 1.82, P = 0.003), POC5/rs2112347 (OR 1.96, P = 2.4E-5), RPS10-NUDT3/rs206936 (OR 1.40, P = 0.023), GLIS3/rs7034200 (OR 2.34, P = 1.2E-6), and VEGFA/rs6905288 (OR 1.58, P = 0.015). The first three were also associated with obesity status. The SNPs POC5/rs2112347 and RPS10-NUDT3/rs206936 were significantly associated through the maternal allele and GLIS3/rs7034200 through the paternal allele (P < 0.05). CONCLUSIONS: These findings suggest that certain SNPs associated with obesity and other metabolic traits may also be involved in risk of pediatric-onset T2D in Mexican families. We also identified preferential transmission of parental alleles in some variants.
Authors: América Liliana Miranda-Lora; Jenny Vilchis-Gil; Daniel B Juárez-Comboni; Miguel Cruz; Miguel Klünder-Klünder Journal: Front Endocrinol (Lausanne) Date: 2021-03-12 Impact factor: 5.555