학술논문
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
Document Type
Article
Author
Berumen, J.; Orozco, L.; Gallardo-Rincón, H.; Juárez-Torres, E.; Barrera, E.; Cruz-López, M.; Benuto, R. E.; Ramos-Martinez, E.; Marin-Madina, M.; Alvarado-Silva, A.; Valladares-Salgado, A.; Peralta-Romero, J. J.; García-Ortiz, H.; Martinez-Juarez, L. A.; Montoya, A.; Alvarez-Hernández, D. A.; Alegre-Diaz, J.; Kuri-Morales, P.; Tapia-Conyer, R.
Source
Journal of Endocrinological Investigation; 20230101, Issue: Preprints p1-13, 13p
Subject
Language
ISSN
03914097; 17208386
Abstract
Purpose: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01microsatellite is near INSand may regulate it. We investigated whether the TH01microsatellite and INSVNTR, 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 TH01and rs689 loci for T2D development; rs689 results were replicated in other case–control (n = 1188) and cross-sectional (n = 1914) studies. Results: TH01alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01alleles 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 TH01alleles 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 TH01alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.