Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

Autor: Berumen J; Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, 06720, Mexico City, México. jaimeberumen47@gmail.com., Orozco L; Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaria de Salud, 14610, Mexico City, México., Gallardo-Rincón H; Departamento de Soluciones Operativas, Fundación Carlos Slim, 11529, Mexico City, Mexico. hgallardo@fundacioncarlosslim.org.; Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, 44340, Guadalajara, Jalisco, México. hgallardo@fundacioncarlosslim.org., Juárez-Torres E; Laboratorio Huella Génica, Unidad de Diabetes, 06600, Mexico City, Mexico., Barrera E; Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, 06720, Mexico City, México., Cruz-López M; Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 06720, Mexico City, México., Benuto RE; Laboratorio Huella Génica, Unidad de Diabetes, 06600, Mexico City, Mexico., Ramos-Martinez E; Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, 06720, Mexico City, México., Marin-Madina M; Laboratorio Huella Génica, Unidad de Diabetes, 06600, Mexico City, Mexico., Alvarado-Silva A; Laboratorio Huella Génica, Unidad de Diabetes, 06600, Mexico City, Mexico., Valladares-Salgado A; Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 06720, Mexico City, México., Peralta-Romero JJ; Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 06720, Mexico City, México., García-Ortiz H; Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaria de Salud, 14610, Mexico City, México., Martinez-Juarez LA; Departamento de Soluciones Operativas, Fundación Carlos Slim, 11529, Mexico City, Mexico.; Center for Humanitarian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Montoya A; Departamento de Soluciones Operativas, Fundación Carlos Slim, 11529, Mexico City, Mexico., Alvarez-Hernández DA; Departamento de Soluciones Operativas, Fundación Carlos Slim, 11529, Mexico City, Mexico., Alegre-Diaz J; Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, 06720, Mexico City, México., Kuri-Morales P; Proyecto OriGen, Instituto Tecnologico y de Estudios Superiores de Monterrey, Monterrey, México., Tapia-Conyer R; Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, 04510, Mexico City, México.
Jazyk: angličtina
Zdroj: Journal of endocrinological investigation [J Endocrinol Invest] 2024 Mar; Vol. 47 (3), pp. 571-583. Date of Electronic Publication: 2023 Aug 25.
DOI: 10.1007/s40618-023-02175-4
Abstrakt: Purpose: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population.
Methods: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies.
Results: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls.
Conclusion: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.
(© 2023. The Author(s).)
Databáze: MEDLINE
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