Typing TREX1 gene in patients with systemic lupus erythematosus

• Main Authors: M. Fredi, M. Bianchi, L. Andreoli, G. Greco, I. Olivieri, S. Orcesi, E. Fazzi, C. Cereda, A. Tincani
• Format: Article
• Language: English
• Published: PAGEPress Publications 2015-06-01
• Series: Reumatismo
• Subjects: TREX1, Novel variation, Neuropsychiatric systemic lupus erythematosus.
• Online Access: http://www.reumatismo.org/index.php/reuma/article/view/782

An impaired expression of interferon-α regulated genes has been reported in patients with either systemic lupus erythematosus (SLE) or Aicardi-Goutières syndrome (AGS), a rare monogenic encephalopathy with onset in infancy. One of mutations causing AGS is located in the <em>TREX1</em> gene on chromosome 3. Heterozygous mutations in <em>TREX1</em> were reported in SLE patients. <em>TREX1</em> is a DNA exonuclease with specificity for ssDNA. An impairment of its activity may result in the accumulation of nucleid acid. A recent study described a significant association between a haplotype including several common single nucleotide polymorphisms (SNPs) of <em>TREX1</em> and neurological manifestations in European SLE patients. Fifty-one SLE patients were screened for <em>TREX1</em> gene, and the corresponding data were collected from clinical charts. A novel heterozygous variant (p.Asp130Asn) was identified in one patient and in none of 150 controls. A missense variation was located in one of the three active sites of the gene and was classified as probably damaging. Variations of SNP rs11797 were detected in 33 SLE patients and a variation of rs3135944 in one. A significantly higher rate of the minor allele (T nucleotide) of SNP rs11797 was found in SLE patients with neuropsychiatric manifestations [12/16 (75%) <em>vs</em> 28/86 (32.5%) O=0.002, odds ratio=6.42 95% confidence interval (1.7-26.2)]. Only 1 out of 8 patients (12.5%) with neuropsychiatric SLE carried the wild-type form in homozygosity. Although we analyzed a small number of patients, we found a novel variation of <em>TREX1</em>, which may be pathogenic. The polymorphism of rs11797 was more frequent in SLE patients with neurological manifestations.