Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study.
BACKGROUND
We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.


METHODS
We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel-Haenszel approach to account for heterogeneity between sample collections.


RESULTS
A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 x 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.


CONCLUSIONS
Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.
Laboratorio de Investigacion 10 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela 15706, Spain. mariansg82@hotmail.com
Marian
M
Suarez-Gestal
Manuel
M
Calaza
Emöke
E
Endreffy
Rudolf
R
Pullmann
Josep
J
Ordi-Ros
Gian Domenico
GD
Sebastiani
Sarka
S
Ruzickova
Maria
M
Jose Santos
Chryssa
C
Papasteriades
Maurizio
M
Marchini
Fotini N
FN
Skopouli
Ana
A
Suarez
Francisco J
FJ
Blanco
Sandra
S
D'Alfonso
Marc
M
Bijl
Patricia
P
Carreira
Torsten
T
Witte
Sergio
S
Migliaresi
Juan J
JJ
Gomez-Reino
Antonio
A
Gonzalez
D016022:Case-Control Studies; D030541:Databases, Genetic / Q000592:standards; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics