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. 2024 Jul 11;15(7):907.
doi: 10.3390/genes15070907.

Genetic Variants of the Receptor Activator Nuclear of κB Ligand Gene Increase the Risk of Rheumatoid Arthritis in a Mexican Mestizo Population: A Case-Control Study

Nava-Valdivia Cesar Arturo  1 , Gamez-Nava Jorge Ivan  2   3 , Contreras-Haro Betsabe  4   5 , Perez-Guerrero Edsaul Emilio  6 , Esparza-Guerrero Yussef  2 , Rodriguez-Jimenez Norma Alejandra  3 , Gonzalez-Heredia Tonatiuh  4 , Villagomez-Vega Alejandra  5 , Nuño-Arana Ismael  5 , Totsuka-Sutto Sylvia Elena  3 , Ponce-Guarneros Juan Manuel  3 , Jacobo-Cuevas Heriberto  3 , Alvarez-Ayala Efren Gerardo  2 , Gonzalez-Lopez Laura  2   3 , Saldaña-Cruz Ana Miriam  3
Affiliations

Genetic Variants of the Receptor Activator Nuclear of κB Ligand Gene Increase the Risk of Rheumatoid Arthritis in a Mexican Mestizo Population: A Case-Control Study

Nava-Valdivia Cesar Arturo et al. Genes (Basel). .

Abstract

The Receptor Activator Nuclear of κB Ligand (RANKL) plays an important function in immune responses, activating osteoclast cells and unchanged bone resorption, which in turn leads to bone erosion and inflammation. Genetic variants in the promoter region of the RANKL gene could lead to a higher risk of rheumatoid arthritis (RA).

Objective: To assess the association of rs9533155 (-693C>G) and rs9533156 (-643T>C) genetic variants with RA risk.

Methods: A case-control study was carried out. A total of 94 patients with RA (RA group) and 134 subjects without any rheumatologic disease (control group) were included. Genetic DNA was extracted from peripheral white blood cells (leukocytes). Genetic variant rs9533155 (-693C>G) was screened by an approach based on Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), while rs9533156 (-643T>C) was screened using quantitative polymerase chain reaction (qPCR) with TaqMan probes. RANKL serum levels were measured by ELISA.

Results: For rs9533155 (-693C>G), the polymorphic homozygous genotype frequencies (CC) were higher in the RA group (p = 0.006). Individuals carrying the risk genotype presented higher levels of serum RANKL. Carriers of the polymorphic homozygous genotype in the dominant model (CC vs. CG + GG) had an increased risk of developing RA (OR: 1.8, 95% CI 1.04 to 3.1). No association between rs9533156 (-643T>C) and the haplotypes with RA risk was observed.

Conclusion: The rs9533155 (-693C>G) genetic variant exhibits a potential role in RA risk. The studied population had no association with the rs9533156 (-643T>C) genetic variant.

Keywords: RANK ligand; genetic variant; rheumatoid arthritis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Comparison of human serum sRANKL concentrations between single-nucleotide polymorphisms (SNP) rs9533155 of RANKL gene. Data are presented as medians and ranges of picomole per liter of sRANKL serum levels (determined by ELISA), for CC (n = 44), CG (n = 29) and GG (n = 21) genotype groups, using the Kruskal–Wallis test. In a comparison between the genotypes in post hoc analysis using the T3-Dunnet test, the p-value was 0.045. (B) Comparison of human serum sRANKL concentrations between single-nucleotide polymorphism (SNP) rs9533156 of RANKL gene. Data are presented as medians and ranges of picomole per liter of sRANKL serum levels (determined by ELISA), for TT (n = 42), TC (n = 39) and CC (n = 13) genotype groups, using the Kruskal–Wallis test.
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