+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6

, : PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6. Annals of the Rheumatic Diseases 74(3): E14-E14

To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.


PMID: 24534757

DOI: 10.1136/annrheumdis-2013-204909

Other references

Park, J.T.e; Mccluggage, M.; Marian, A.J., 1999: Human CSX-1 activates alpha-myosin heavy chain promoter by binding to sp1 sequences in intron 2. Circulation 100(18 SUPPL ): I 355, Nov 2

Girinsky, T.; Rey, A.; Roche, B.; Haie, C.; Gerbaulet, A.; Randrianarivello, H.; Chassagne, D., 1993: Overall treatment time in advanced cervical carcinomas: A critical parameter in treatment outcome. Purpose: To search for possible influence of overall treatment time on the clinical outcome of advanced cervical carcinomas treated with radiation alone. Methods and Materials: Three hundred and eighty-six patients with Stage IIB and III cervical...

Profet M., 1988: The evolution of pregnancy sickness as protection to the embryo against pleistocene teratogens. Pregnancy sickness may have evolved during the Pleistocene as a protection to the embryo against the wide array of toxic foods available to the mother. The nausea and food aversions that characterize pregnancy sickness deter pregnant women from co...

Nguyen, V.K.; Bourges, N.; Concordet, D.; Dorchies, P., 1996: Mast cells and eosinophils in respiratory mucosa of sheep infected with Oestrus ovis (Linne, 1761) larvae. Mast cells and eosinophils were identified by differential staining and counted in the mucous membrane of the nasal septum, turbinates and sinus of 77 ewes naturally infected with O. ovis in 1994-95 in France. Results were compared with those of 9...

Anonymous, 1974: The Australian National Animal Health Laboratory. Australian Veterinary Journal 50(10): 467-470

Wolpaw, B.J.; Mathews, C.; Chopra, M.; Hardie, D.; Lurie, M.N.; Jennings, K., 2011: Diagnosis and counselling of patients with acute HIV infection in South Africa. To identify, diagnose and counsel patients with acute HIV infection (AHI) during routine HIV testing in South Africa. Patients with sexually transmitted infection and clients undergoing voluntary counselling and testing who were negative on rapid...

Zaĭtseva, E.I.; Khokhlova, L.T., 1978: Use of bromsulfane-I131 for diagnosis of diseases of the hepatobiliary system. Meditsinskaia Radiologiia 23(4): 72-75

Cape, E.G.; Thomas, J.D.; Weyman, A.E.; Yoganathan, A.P.; Levine, R.A., 1995: Three-dimensional surface geometry correction is required for calculating flow by the proximal isovelocity surface area technique. This study addressed the hypothesis that surface geometry must be taken into account in proximal convergence calculations of regurgitant flow rate. In vitro models allowed flow to converge within models designed to test derived angle correction eq...

Jafri S.I.H.; Ensor D.M., 1983: The morphology and histology of the pineal organ in roach rutilus rutilus. The pineal organ in the roach, R. rutilus is covered by a semi-transparent area, the pineal window. Beneath this the pineal is attached to a long robust stalk, lying just under the parietal bone. The pineal is attached to the brain through the dor...

Kamani, N.; Douglas, S.D., 1988: Natural history of chronic granulomatous disease. An analysis of the patient characteristics, clinical course, and therapy of 52 patients with chronic granulomatous disease (CGD) was carried out through a multinstitutional questionnaire survey in order to further define the natural history of thi...