A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14.

OBJECTIVE: More than 40 loci have been associated with ankylosing spondylitis (AS), but less is known about genetic associations in spondyloarthritis (SpA) as a whole. We conducted a family-based genome-wide association study (GWAS) to identify new non-major histocompatibility complex (MHC) genetic factors associated with SpA. METHODS: 906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays. Association was tested with Unphased. The best-associated non-MHC single nucleotide polymorphisms (SNPs) were then genotyped in two independent familial cohorts (including 215 French and 294 North American patients with SpA, respectively) to replicate associations. RESULTS: 43 non-MHC SNPs yielded an association signal with SpA in the discovery cohort (p<1×10-4). In the extension studies, association was replicated at a nominal p value of p<0.05 for 16 SNPs in the second cohort and for three SNPs in the third cohort. Combined analysis identified an association close to genome-wide significance between rs7761118, an intronic SNP of MAPK14, and SpA (p=3.5×10-7). Such association appeared to be independent of HLA-B27. CONCLUSIONS: We report here for the first time a family-based GWAS study on SpA and identified an associated polymorphism near MAPK14. Further analyses are needed to better understand the functional basis of this genetic association.

Klinefelter's syndrome (47,XXY) among men with systemic lupus erythematosus.

AIM: To determine the rate of Klinefelter's syndrome among men with systemic lupus erythematosus (SLE), and to determine whether the manifestations of SLE in these men are different from that seen in 46,XY men. METHODS: A total of 276 men with SLE underwent a real-time PCR procedure to screen for more than one X chromosome. Those with results consistent with two X chromosomes were further characterized by karyotype and FISH. Clinical manifestations of SLE were determined by interview, questionnaire and medical chart review. Each man with Klinefelter's and SLE was matched to four 46,XY men with SLE. Rates of SLE manifestations were compared with chi-square analyses. RESULTS: We found seven of the 286 men with SLE had Klinefelter's syndrome. Four of these seven were nonmosaic 47,XXY, while two were mosaic 46,XY/47,XXY and one was 46,XX/47,XXY. The men with 47,XXY did not have severe manifestations of SLE including no proliferative renal disease, neurological disease, thrombocytopenia, autoimmune haemolytic anaemia, discoid skin disease or anti-RNP/Sm. CONCLUSION: 47,XXY is found in excess among men with SLE. Men commonly have SLE that is more severe than that found among women, but the 47,XXY men had less severe SLE than other men.