The -844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE.
FasL expression is critical in T-cell activation-induced apoptosis, which is involved in lupus pathogenesis. This study identified two SNPs in the FasL promoter regions from -1145 to -45 by genomic DNA sequencing. The -844C/T polymorphism was previously described by its location in and affect on the CCAAT/enhancer-binding protein beta (C/EBPB beta)-binding site and the other (-1094A/C, a novel polymorphism) was located at the NF-kappaB transcription-binding site. FasL gene promoter polymorphisms were genotyped in 260 systemic lupus erythematosus (SLE) patients and 280 healthy controls using MassArray matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. The distribution of FasL promoter -844C/C genotype, predominant in Taiwanese, was skewed in Taiwanese SLE patients (odds ratio: 1.53; P-value=0.014). FasL promoter -844C/T polymorphism genotype distributions of Taiwanese, African Americans, and Caucasians differed. Moreover, no particular clinical association of -844C/T and -1094A/C polymorphisms with SLE was found in patients in Taiwan. This study confirmed that -844C/C genotype is associated with lupus susceptibility. The -1094A/C polymorphism is not significantly associated with lupus disease susceptibility, albeit the role of NF-kappaB pathway in FasL promoter activation remains unclear. Fas/FasL pathway may contribute to SLE polygenic disease entity.
Chen
J-Y
JY
Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Taiwan, Republic of China. jychen31@adm.cgmh.org.tw
Wang
C-M
CM
Ma
C-C
CC
Chow
Y-H
YH
Luo
S-F
SF
D044466:Asian People; D053222:Fas Ligand Protein; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D013624:Taiwan
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins