A multilocus genetic study in a cohort of Italian SLE patients confirms the association with STAT4 gene and describes a new association with HCP5 gene.

Abstract

BACKGROUND:

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex pathogenesis in which genes and environmental factors are involved. We aimed at analyzing previously identified loci associated with SLE or with other autoimmune and/or inflammatory disorders (STAT4, IL10, IL23R, IRAK1, PSORS1C1, HCP5, MIR146a, PTPN2, ERAP1, ATG16L1, IRGM) in a sample of Italian SLE patients in order to verify or confirm their possible involvement and relative contribution in the disease.

MATERIALS AND METHODS:

Two hundred thirty-nine consecutive SLE patients and 278 matched healthy controls were enrolled. Study protocol included complete physical examination, and clinical and laboratory data collection. Nineteen polymorphisms were genotyped by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed.

RESULTS:

STAT4 was the most associated gene [P = 3 × 10(-7), OR = 2.13 (95% CI: 1.59-2.85)]. IL10 confirmed its association with SLE [rs3024505: P = 0.02, OR = 1.52 (95% CI: 1.07-2.16)]. We describe a novel significant association between HCP5 locus and SLE susceptibility [rs3099844: P = 0.01, OR = 2.06 (95% CI: 1.18-3.6)]. The genotype/phenotype correlation analysis showed several associations including a higher risk to develop pericarditis with STAT4, and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies.

CONCLUSIONS:

STAT4 and IL10 confirm their association with SLE. We found that some SNPs in PSORS1C1, ATG16L1, IL23R, PTPN2 and MIR146a genes can determine particular disease phenotypes. HCP5 rs3099844 is associated with SLE and with anti-Ro/SSA. This polymorphism has been previously found associated with cardiac manifestations of SLE, a condition related with anti-Ro/SSA antibodies. Thus, our results may provide new insights into SLE pathogenesis.

• Authors: Cinzia Ciccacci, Carlo Perricone, Fulvia Ceccarelli, Sara Rufini, Davide Di Fusco, Cristiano Alessandri, Francesca Romana Spinelli, Enrica Cipriano, Giuseppe Novelli, Guido Valesini, Paola Borgiani, Fabrizio Conti
• Journal: PloS one (PLoS One) Vol. 9 Issue 11 Pg. e111991 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25369137 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• HCP5 long noncoding RNA, human
• PSORS1C1 protein, human
• Proteins
• RNA, Long Noncoding
• RNA, Untranslated
• STAT4 Transcription Factor
• STAT4 protein, human

Topics

• Adult
• Autoantibodies (blood)
• Case-Control Studies
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Italy
• Lupus Erythematosus, Systemic (blood, genetics, immunology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Proteins (genetics)
• RNA, Long Noncoding
• RNA, Untranslated (genetics)
• STAT4 Transcription Factor (genetics)