Comparison of Mexican Ethnic Groups Shows Genetic Factors Heighten SLE Risk

A new comparison of genetic factors among 2 Mexican ethnic groups highlights the role of toll-like receptor7 (TLR7) in the pathogenesis of systemic lupus erythematosus (SLE).

Corresponding author Guillermo Valencia Pacheco, MD, PhD, of the Autonomous University of Yucatán in Mexico, and colleagues wrote that while SLE is found all over the world, its prevalence varies from one population to the next.

“Genetics play a role in the susceptibility to develop SLE, and the number of candidate genes associated with SLE has increased with the analysis of the human genome,” they explained.

In the new study, published in the Journal of Immunology Research, the investigators looked at how genetic factors affect SLE risk in 2 distinct Mexican populations. The authors noted that Mexico’s mestizo population has at least 3 genetic origins: Amerindian, Caucasian, and African. However, the mestizo of the Yucatán region (Yucatecans) are distinct because their Amerindian genetics are primarily Mayan.

The investigators decided to analyze 2 specific genetic factors within Yucatecan women and compare them with women from Central Mexico, where the genetics of the population are more diverse. The factors chosen were copy-number variation (CNV) and the frequency of the single nucleotide polymorphism (SNP) rs179008 of TLR7. CNV of certain genes, including TLR7, has been linked with SLE risk. The SNP rs179008 has been linked with higher production of interferon alpha, which has been linked to the pathogenesis of SLE.

The authors analyzed 100 DNA samples from Yucatecan women with SLE and compared them with 102 samples from healthy volunteers from Yucatán. In addition, they collected 151 DNA samples from women with SLE in the central region of Mexico, as well as 121 samples from healthy controls. The women in the latter group represented several different ethnic groups.

The analysis showed that Yucatecan subjects were significantly more likely to have more than 2 copies of TLR7, which in turn was associated with a greater risk of developing SLE, the authors said.

“We observed that 14% of Yucatecan patients showed significantly >2 CNV compared to 4% of those in Central Mexico and 34.36 times more at risk for developing the disease,” Pacheco and colleagues wrote.

However, when they examined the risk of allele T and wild allele A, they found the T allele was less common in the Yucatecan population.

“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, and association with susceptibility to develop SLE was observed,” the authors said.

They added, however, that rs179008 may not be the only SNP affecting SLE risk in these populations.

“[W]e cannot exclude other SNPs of the TLR7 that may be contributing to the development of SLE since the rs179008 is in a region of known CNV, and alleles may differ with the number of copies,” they added.

The investigators said these data confirm that genetic factors can play a major role in SLE risk, even within a single country.

“The susceptibility for developing SLE results from the interaction of multiple genes and environmental factors; however, ethnicity plays a vital role in its development, and the Amerindian population is more susceptible to developing it,” they concluded.

Reference:

Pacheco GV, Ueji YEN, Bello JR, et al. Copy number variation and frequency of rs179008 in TLR7 gene associated with systemic lupus erythematosus in two Mexican populations. J Immunol Res. Published online January 17, 2022. doi:10.1155/2022/2553901