Copy Number Variation and Frequency of rs179008 in TLR7 Gene Associated with Systemic Lupus Erythematosus in Two Mexican Populations.

Guillermo Valencia Pacheco,Eduardo D Jiménez Becerra,Gerardo J Pérez Mendoza,Nubia A Rivero Cárdenas,Yumi E Nakazawa Ueji,Lizbeth J González Herrera,Julián Ramírez Bello,Rosa E Barbosa Cobos,Ricardo F López Villanueva,Angélica V Angulo Ramírez,Carlo Perricone

doi:10.1155/2022/2553901

Abstract

Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.

Highlights

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown etiology, characterized by hyperactivity of B lymphocytes and the presence of antiDNA autoantibodies, which affects women of reproductive age
Genetics play a role in the susceptibility to develop SLE, and the number of candidate genes associated with SLE has Journal of Immunology Research increased with the analysis of the human genome [9,10,11]; some are involved in the recognition of nucleic acids and production of interferons (IFN) [12, 13] while others are participating in T and B-cell signaling pathways [14, 15]
This is the first study comparing women with SLE from two Mexican populations; the Yucatecan from various municipalities of the Yucatán State with an essential contribution of Mayan ancestry, and from Central Mexico coming from the different Central States of the country (Mexico State, Guerrero, Queretaro, Oaxaca, Tlaxcala), which represent the ethnic heterogeneity in the last population

Summary

Introduction

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown etiology, characterized by hyperactivity of B lymphocytes and the presence of antiDNA autoantibodies, which affects women of reproductive age. It is a disease of universal distribution whose incidence and prevalence vary among populations [1,2,3,4,5,6]. CNV arises when a complete gene or segment of it is duplicated, having more than two copies, or when is deleted. Additional copies of these genes can promote overexpression of proteins, and its deletion leads to deficiency and functional changes [16]

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