Replication of the association between the C8orf13-BLK region and systemic lupus erythematosus in a Japanese population.
OBJECTIVE
Recent genome-wide association studies identified an association between single-nucleotide polymorphisms (SNPs) in the C8orf13 region of BLK, the B lymphoid tyrosine kinase gene, with systemic lupus erythematosus (SLE) in Caucasians. The purpose of this study was to evaluate the significance of this region in the genetic background of Japanese patients with SLE.


METHODS
Fourteen tag SNPs in the C8orf13-BLK region were genotyped in 327 Japanese patients with SLE and 322 healthy Japanese controls. The population-attributable risk percentage (PAR%) of rs13277113 in Japanese was compared with that in Caucasians as well as with that of other SLE susceptibility genes in Japanese.


RESULTS
As in Caucasians, rs13277113A demonstrated the strongest association in Japanese (P = 1.73 x 10(-6) for the genotype frequency, P = 4.75 x 10(-7) for the allele frequency, odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.43-4.16]). The association in Japanese was consistent with a recessive model (P = 2.74 x 10(-7), OR 2.27 [95% CI 1.66-3.11]). In contrast to the Caucasian population, this risk allele was the major allele in the Japanese population. Because both the risk allele frequency and the OR were higher in Japanese than in Caucasians, the PAR% of rs13277113 was estimated to be much higher in Japanese (35.4%) than in Caucasians (16.2%), and the second highest among the 6 confirmed SLE susceptibility genes in Japanese.


CONCLUSIONS
The association of the C8orf13-BLK region with SLE was replicated in a Japanese population. Contribution of this region to the genetic predisposition to SLE appeared to be greater in Japanese than in Caucasians.
Ito
Ikue
I
University of Tsukuba, Tsukuba, Japan.
Kawasaki
Aya
A
Ito
Satoshi
S
Hayashi
Taichi
T
Goto
Daisuke
D
Matsumoto
Isao
I
Tsutsumi
Akito
A
Hom
Geoffrey
G
Graham
Robert R
RR
Takasaki
Yoshinari
Y
Hashimoto
Hiroshi
H
Ohashi
Jun
J
Behrens
Timothy W
TW
Sumida
Takayuki
T
Tsuchiya
Naoyuki
N
D044466:Asian People / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics*
D019061:src-Family Kinases