B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren's syndrome

Adrianos Nezos; Aristea Papageorgiou; George Fragoulis; Dimitrios Ioakeimidis; Michael Koutsilieris; Athanasios G Tzioufas; Haralampos M Moutsopoulos; Michael Voulgarelis; Clio P Mavragani

doi:10.1016/j.jaut.2013.04.005

B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren's syndrome

J Autoimmun. 2014 Jun:51:89-98. doi: 10.1016/j.jaut.2013.04.005. Epub 2013 Jul 9.

Authors

Adrianos Nezos¹, Aristea Papageorgiou², George Fragoulis², Dimitrios Ioakeimidis³, Michael Koutsilieris¹, Athanasios G Tzioufas², Haralampos M Moutsopoulos², Michael Voulgarelis², Clio P Mavragani⁴

Affiliations

¹ Department of Physiology, School of Medicine, University of Athens, Athens, Greece.
² Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece.
³ Department of Rheumatology, General Hospital of Athens "G.Gennimatas", Athens, Greece.
⁴ Department of Physiology, School of Medicine, University of Athens, Athens, Greece. Electronic address: kmauragan@med.uoa.gr.

PMID: 23845207
DOI: 10.1016/j.jaut.2013.04.005

Abstract

Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients. Several clinical and serological features are proposed as adverse predictors for such complication and define a high risk pSS phenotype. We aimed to explore whether previously described polymorphisms of the B-cell activating factor (BAFF) could be related to pSS-related lymphomagenesis. Five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated in 111 low risk pSS patients (type II), 82 high risk/lymphoma patients (type I) and 137 healthy controls (HC) by PCR-based assays. The classification of pSS patients into types I and II was based on the presence or absence of risk factors or lymphoma development, respectively. Genotype and haplotype analysis was performed for all variants in the pSS groups. Since the rs1041569 SNP was not in Hardy-Weinberg equilibrium in the HC group (p < 0.001), haplotype analysis was performed in the remaining four out of the five SNPs tested when comparisons with HC individuals were performed. The high risk pSS group was characterized by higher frequency of the minor T allele of the rs9514828 BAFF polymorphism compared to HC. Compared to the low risk pSS patients but not the HC, the high risk pSS group exhibited lower frequencies of the AA genotype of the rs12583006 polymorphism as well as the TACAC and TACC haplotypes and higher frequency of the TTTC haplotype. The low risk pSS group exhibited higher frequency of the minor A allele and AA genotype of the rs12583006 variant compared to HC. Both pSS groups were characterized by increased frequency of the haplotype TATT and GTTC and decreased frequency of the TTCT when compared to HC. Taken together, these findings suggest the implication of the host's genetic background in pSS-related lymphomagenesis. The interaction of pSS-related BAFF gene haplotypes together with distinct BAFF genetic variants appears to contribute to this complication.

Keywords: B-lymphocyte activator factor (BAFF); Genetics; Lymphoma; Primary Sjogren's syndrome (SS); Single nucleotide polymorphisms (SNPs).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
B-Cell Activating Factor / genetics*
Case-Control Studies
Cell Transformation, Neoplastic / genetics*
Gene Frequency
Gene Order
Genetic Loci
Genetic Variation*
Genotype
Haplotypes
Humans
Lymphoma / diagnosis
Lymphoma / etiology*
Polymorphism, Single Nucleotide
Sjogren's Syndrome / complications*
Sjogren's Syndrome / diagnosis
Sjogren's Syndrome / genetics*

Substances

B-Cell Activating Factor