ITGAM is a risk factor to systemic lupus erythematosus and possibly a protection factor to rheumatoid arthritis in patients from Mexico


Autoři: Julian Ramírez-Bello aff001;  Celi Sun aff002;  Guillermo Valencia-Pacheco aff003;  Bhupinder Singh aff002;  Rosa Elda Barbosa-Cobos aff004;  Miguel A. Saavedra aff005;  Ricardo F. López-Villanueva aff006;  Swapan K. Nath aff002
Působiště autorů: Research Unit, Hospital Juárez de México, Mexico City, Mexico aff001;  Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America aff002;  Hematology Laboratory, Regional Research Center, Autonomous University of Yucatan, Yucatan, Mexico aff003;  Rheumatology Department, Hospital Juárez de México, Mexico City, Mexico aff004;  Rheumatology Department, Centro Médico Nacional “La Raza”, Mexico City, Mexico aff005;  Rheumatology Department, Regional Hospital General (ISSSTE), Health Service Yucatan, Yucatan, Mexico aff006
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224543

Souhrn

Introduction

ITGAM has consistently been associated with susceptibility to systemic lupus erythematosus (SLE) in many ethnically diverse populations. However, in populations with higher Amerindian ancestry (like Yucatan) or highly admixed population (like Mexican), ITGAM has seldom been evaluated (except few studies where patients with childhood-onset SLE were included). In addition, ITGAM has seldom been evaluated in patients with rheumatoid arthritis (RA). Here, we evaluated whether four single nucleotide polymorphisms (SNPs), located within ITGAM, were associated with SLE and RA susceptibility in patients from Mexico.

Methods

Our study consisted of 1,462 individuals, which included 363 patients with SLE (292 from Central Mexico and 71 from Yucatan), and 621 healthy controls (504 from Central Mexico and 117 from Yucatan). Our study also included 478 patients with RA from Central Mexico. TaqMan assays were used to obtain the genotypes of the four SNPs: rs34572943 (G/A), rs1143679 (G/A), rs9888739 (C/T), and rs1143683 (C/T). We also verified the genotypes by Sanger sequencing. Fisher's exact test and permutation test were employed to evaluate the distribution of genotype, allele, and haplotype between patients and controls.

Results

Our data show that all four ITGAM SNPs are significantly associated with susceptibility to SLE using both genotypic and allelic association tests (corrected for multiple testing, but not for population stratification). A second study carried out in patients from Yucatan, a southeastern part of Mexico (with a high Amerindian ancestry), also replicated SLE association with all four SNPs, including the functional SNP, rs1143679 (OR = 24.6 and p = 9.3X10-6). On the other hand, none of the four SNPs are significant in RA after multiple testing. Interestingly, the GACC haplotype, which carries the ITGAM rs1143679 (A) minor allele, showed an association with protection against RA (OR = 0.14 and p = 3.0x10-4).

Conclusion

Our data displayed that ITGAM is a risk factor to SLE in individuals of Mexican population. Concurrently, a risk haplotype in ITGAM confers protection against RA.

Klíčová slova:

Genome-wide association studies – Haplotypes – Mexican people – Mexico – Molecular genetics – Rheumatoid arthritis – Variant genotypes


Zdroje

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