Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in rheumatoid arthritis

Abstract

Objective-The aim of this study was to investigate the relation between the polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and rheumatoid arthritis (RA). Methods-Sixty RA patients and 102 ethnically matched unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA-DRB1 alleles by using a new strategy based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with amplification created restriction sites. Results-The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1-TAP2) genes was examined in shared epitope positive and negative RA patients and controls. No significant diVerences in the LMP or TAP allele frequencies were observed between the total patient and control groups or the patients and controls positive or negative for the shared epitope. Conclusion-The data suggest that the polymorphisms of LMP and TAP genes do not have an important influence in the pathogenesis of RA, although larger studies will be needed to provide more conclusive evidence on the role of these genes in RA. A new, highly reliable strategy for typing LMP alleles is also described.

LMP2 and LMP7 gene polymorphism in Mexican populations: Mestizos and Amerindians

“…The frequencies were compared among them and with other previously described frequencies in other populations. 6,12,20 LMP2 and LMP7 allele and genotype frequencies distribution were similar among Mexicans, except on Nahuas and Mayos that bear the highest frequencies of LMP2-H/H genotype when compared with Mexican Mestizos, Mazatecans and Teenek populations. Despite the similarities among the groups, these data suggest that the differences in frequencies of LMP2 genotypes could be helpful in distinguishing each of these populations particularly when they belong to different linguistic trunks.…”

“…[6][7][8][9][10][11] Thus, the detailed distribution of LMP alleles in Mexican populations could help define the participation of this polymorphism in the genetic susceptibility for certain diseases. Few data related to the participation of LMP polymorphism in the genetic susceptibility to develop autoimmune disease have been reported.…”

“…Some of them include diseases such as ankylosing spondylitis (AS), rheumatoid arthritis (RA) and insulin-dependent dia-betes mellitus (IDDM). [6][7][8] However, positive association has only been detected in patients with AS. 8 In the Mexican population the LMP2-H allele has been associated with acute anterior uveitis (AAU) in AS patients.…”

“…Diseases studied in relation to the possible participation of these genes as genetic markers include rheumatoid arthritis (RA), insulin-dependent diabetes mellitus (IDDM) and ankylosing spondylitis (AS). [6][7][8] However, several reports show lack of association or conclude that this association might be secondary to linkage disequilib- rium with HLA genes primary associated with the disease. [9][10][11] Studies of associations with diseases across ethnic groups are important in removing the confounding effects of linkage disequilibrium and are helpful to localize the actual disease-conferring alleles.…”

“…Population studies of LPM polymorphism are rare and the majority refers mostly to Caucasian and Oriental populations. 6,8,9,12 In an effort to define genetic admixture in Mexican Mestizos, this ethnic group has been characterized by using genetic markers from several chromosomes. Results from these studies have shown a proportion of 56% Amerindian genes, 40% Caucasian genes, and 4% black genes.…”