Analysis of the association between PTPN1 gene polymorphisms (rs941798 and rs914458) and type 2 diabetes in families from Lima – Peru
DOI:
https://doi.org/10.24265/horizmed.2019.v19n4.03Keywords:
Diabetes mellitus type 2, Non-receptor protein tyrosine phosphatase type 1, Genetic markers, Single nucleotide polymorphismAbstract
Objective: To analyze the association that PTPN1 gene single nucleotide polymorphisms (SNPs) rs941798 and rs914458 have with type 2 diabetes in Peruvian families from Lima. Materials and methods: Twenty-three (23) families consisting of three members each were recruited at the Hospital Nacional Arzobispo Loayza. Peripheral blood samples were collected to obtain the DNA, and then the allele and genotype frequencies of the SNPs. SNP genotyping was performed using the sequencing method. The family-based analysis of the association between SNPs and type 2 diabetes was conducted using the family-based association test (FBAT) program. Results: Three (3) possible genotypes were observed for each SNP, i.e. rs941798 (A>G) and rs914458 (G>C). In one of the assessed models, the family-based association tests showed at the allele level that allele A of SNP rs941798 is associated with type 2 diabetes (p = 0.023). However, after using the Bonferroni correction for multiple comparisons, this association was lost. No association was demonstrated between the SNPs and the disease at any level (allele, genotype or haplotype). Conclusions: No evidence of significant association was found between PTPN1 gene SNPs rs941798 and rs914458 and type 2 diabetes at the studied levels (allele, genotype or haplotype) in Peruvian families from Lima.
Downloads
References
International Diabetes Federation. IDF Diabetes Atlas. 8th edition. Brussels: International Diabetes Federation; 2017.
Ministerio de Salud del Perú. Análisis de las causas de mortalidad en el Perú, 1986-2015. 1ra edición. Lima: Ministerio de Salud del Perú; 2018. 226 p.
Villena JE. Epidemiología de la diabetes mellitus en el Perú. Diagnóstico. 2016; 55(4): 173-81.
Kwak SH, Park KS. Recent progress in genetic and epigenetic research on type 2 diabetes. Exp Mol Med. 2016; 48(3): e220.
Beagley J, Guariguata L, Weil C, Motala AA. Global estimates of undiagnosed diabetes in adults. Diabetes Res Clin Pract. 2014; 103(2): 150-60.
Kalyani RR, Saudek CD, Brancati FL, Selvin E. Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Diabetes care. 2010; 33(5): 1055-60.
American Diabetes Association. Standards of medical care in diabetes-2016 abridged for primary care providers. Clin Diabetes. 2016; 34(1): 3-21.
Gurzov EN, Stanley WJ, Brodnicki TC, Thomas HE. Protein tyrosine phosphatases: molecular switches in metabolism and diabetes. Trends Endocrinol Metab. 2015; 26(1): 30-9.
Feldhammer M, Uetani N, Miranda-Saavedra D, Tremblay ML. PTP1B: a simple enzyme for a complex world. Crit Rev Biochem Mol Biol. 2013; 48(5): 430-45.
Sun J, Qu C, Wang Y, Huang H, Zhang M, Li H, et al. PTP1B, a potential target of type 2 Diabetes Mellitus. Mol Biol. 2016; 5(4): 174.
Tsou RC, Bence KK. The Genetics of PTPN1 and Obesity: insights from mouse models of tissue-specific PTP1B deficiency. J Obes. 2012; 2012: 1-8.
Di Paola R, Frittitta L, Miscio G, Bozzali M, Baratta R, Centra M, et al. A variation in 3′ UTR of hPTP1B increases specific gene expression and associates with insulin resistance. Am J Hum Genet. 2002; 70(3): 806-12.
Palmer ND, Bento JL, Mychaleckyj JC, Langefeld CD, Campbell JK, Norris JM, et al. Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans: the insulin resistance atherosclerosis study (IRAS) family study. Diabetes. 2004; 53(11): 3013-9.
Cheyssac C, Lecoeur C, Dechaume A, Bibi A, Charpentier G, Balkau B, et al. Analysis of common PTPN1 gene variants in type 2 diabetes, obesity and associated phenotypes in the French population. BMC Med Genet. 2006; 7(1): 44.
Bento JL, Palmer ND, Mychaleckyj JC, Lange LA, Langefeld CD, Rich SS, et al. Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes. Diabetes. 2004; 53(11): 3007-12.
Hawley M, Kidd KK. HAPLO: a program using the EM algorithm to estimate the frequencies of multi-site haplotypes. J Hered. 1995; 86(5): 409-11.
Rabinowitz D, Laird NM. A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Hum Hered. 2000; 50(4): 211-23.
Laird NM, Horvath S, Xu X. Implementing a unified approach to family-based tests of association. Genet Epidemiol. 2000; 19(Suppl.1): 36-42.
Horvath S, Xu X, Laird NM. The family based association test method: strategies for studying general genotype-phenotype associations. Eur J Hum Genet. 2001; 9(4): 301-6.
Prasad RB, Groop L. Genetics of type 2 diabetes-pitfalls and possibilities. Genes (Basel). 2015; 6(1): 87-123.
Vassy JL, Hivert MF, Porneala B, Dauriz M, Florez JC, Dupuis J, et al. Polygenic type 2 diabetes prediction at the limit of common variant detection. Diabetes. 2014; 63(6): 2172-82.
Florez JC, Agapakis CM, Burtt NP, Sun M, Almgren P, Råstam L, et al. Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people. Diabetes. 2005; 54(6): 1884-91.
Paredes Anaya M, García-Quispes WA, Lizaraso Soto F, Padilla Rojas C, Torres-Gonzales D, Calderón Ticona J, et al. Análisis de asociación genética entre el SNP RS914458 del gen proteína tirosina fosfatasa no receptor tipo 1 (PTPN1) y diabetes tipo 2 en población peruana. Horiz Med. 2014; 14(4): 31-6.
Ghosh S, Watanabe RM, Hauser ER, Valle T, Magnuson VL, Erdos MR, et al. Type 2 diabetes: evidence for linkage on chromosome 20 in 716 finnish affected sib pairs. Proc Natl Acad Sci USA. 1999; 96(5): 2198–203.
Traurig M, Hanson RL, Kobes S, Bogardus C, Baier LJ. Protein tyrosine phosphatase 1B is not a major susceptibility gene for type 2 diabetes mellitus or obesity among Pima Indians. Diabetología. 2007; 50(5): 985–9.
Bodhini D, Radha V, Ghosh S, Majumder PP, Mohan V. Lack of association of PTPN1 gene polymorphisms with type 2 diabetes in South Indians. J Genet. 2011; 90(2): 323–6.
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Horizonte Médico (Lima)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Horizonte Médico (Lima) (Horiz. Med.) journal’s research outputs are published free of charge and are freely available to download under the open access model, aimed at disseminating works and experiences developed in biomedical and public health areas, both nationally and internationally, and promoting research in the different fields of human medicine. All manuscripts accepted and published in the journal are distributed free of charge under the terms of a Creative Commons license – Attribution 4.0 International (CC BY 4.0).
