Fas ligand gene polymorphisms are not associated with Hashimoto’s thyroiditis and Graves’ disease

Stuck, Bettina J.; Pani, Michael A.; Besrour, Foued; Segni, Maria; Krause, Maren; Usadel, K. H.; Badenhoop, Klaus

doi:10.1016/s0198-8859(02)00775-9

Cited by 22 publications

(13 citation statements)

References 20 publications

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“…In contrast, À844C/C genotype did not increase disease susceptibility risk in Caucasians in previous studies of autoimmune-related diseases, including SLE, type I insulin-independent diabetes mellitus, and autoimmune thyroid diseases. 31,[36][37][38] Moreover, the frequency of -844C/T polymorphism was not significantly different in patients with positive vs negative clinical manifestations and autoantibodies. These findings indicate that lupus pathogenesis is complex and multiple genetic defects might be required for development of the full-blown disease.…”

Section: Discussionmentioning

confidence: 83%

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

Chen¹,

Wang²,

Chi³

et al. 2005

Genes Immun

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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 b (C/EBPB b)-binding site and the other (-1094A/C, a novel polymorphism) was located at the NF-kB 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 ¼ 0.014). FasL promoter À844C/T polymorphism genotype distributions of Taiwanese, African Americans, and Caucasians differed. Moreover, no particular clinical association of À844C/T and À1094A/C polymorphisms with SLE was found in patients in Taiwan. This study confirmed that À844C/C genotype is associated with lupus susceptibility. The -1094A/C polymorphism is not significantly associated with lupus disease susceptibility, albeit the role of NF-kB pathway in FasL promoter activation remains unclear. Fas/FasL pathway may contribute to SLE polygenic disease entity.

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Section: Discussionmentioning

confidence: 83%

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

Chen¹,

Wang²,

Chi³

et al. 2005

Genes Immun

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“…There is strong evidence demonstrating that decreased expression of FAS may protect transformed cells from elimination by antitumor immune responses, and increased expression of FASLG may increase the ability of tumor cells to counter-attack the immune system by killing FAS-sensitive lymphocytes, thereby contributing to cancer development [44]. To date, several association studies have reported that the FAS and FASLG polymorphisms are associated with risk of diseases, including cancer and systemic lupus erythematosus, in different ethnic groups [14][15][16]20,23,44,45]. Furthermore, functional germline and somatic mutations in the FAS gene, and perhaps also in the FASLG gene, that impair apoptotic signal transduction are associated with susceptibility to cancers, including CMM [12].…”

Section: Discussionmentioning

confidence: 99%

“…In FASLG, a T to C transition at position -844 in the promoter region has been reported to be located in a binding motif for another transcription factor, the CAAT/enhancer binding protein b25, and higher basal expression of FASLG is significantly associated with the FASLG-844C allele compared to the -844 T allele [15]. Another polymorphic site of FASLG is an A to G substitution exits in the second intron at position 124 upstream from the first base of the third exon, known as FASLG-IVS2nt-124 [16]. It was found that this polymorphism might have an effect on the expression of the FASLG gene [17].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

Larson

Zhang

et al. 2006

Pharmacogenetics and Genomics

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The FAS/FAS ligand (FASLG) system has a key role in regulating cell growth and thus tumorigenesis. Functional promoter polymorphisms of the FAS and FASLG genes alter the transcriptional activities, but no published study has investigated the role of these polymorphisms in the etiology of cutaneous malignant melanoma (CMM). In a hospital-based, case-control study of 602 non-Hispanic white CMM patients and 603 cancer-free age- and sex-matched control subjects, we genotyped FAS-1377G>A, FAS-670A>G, FASLG-844T>C and FASLG-IVS2nt-124G>A polymorphisms and assessed their respective associations with CMM risk. We found that an increased risk of CMM was associated with the FAS-1377GG [adjusted odds ratio (OR)=1.32; 95% confidence interval (CI)=1.00-1.75 for -1377GG] and -670AA (adjusted OR=1.28; 95% CI=1.00-1.65 for -670AA) genotypes compared to the -1377AA/AG and -670AG/GG genotypes, respectively; an increased risk of CMM was associated with the FASLG-IVS2nt-124AG+GG (OR=1.54; 95% CI=1.18-2.01) genotype compared to the AA genotype, but no evident risk was associated with any of the FAS-844T>C genotypes. In the combined analysis of these four variant alleles, we found that, compared to those having 0-3 variants, those having 4-8 variant alleles had a significantly increased risk for CMM (OR=1.38; 95% CI=1.10-1.73), and this risk was more pronounced in subgroups of old (>50 years) males, and those who were at low risk of sunlight-induced CMM, except for having fair skin colour, moles, dysplastic nevi and a family history of cancer. In conclusion, genetic variants in the FAS and FASLG genes may contribute to the etiology of CMM in the general population, particularly in those with a low risk of sunlight-induced CMM.

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“…FAS and FASLG polymorphisms were identified by using the PCR-RFLP method, as previously described (27). The following primers were used to amplify the target fragments containing these four polymorphisms (mismatch bases are underlined): 5 ¶-TGTGTGCACAAGGCTGGCGC-3 ¶ (forward) and 5 ¶-TGCATCTGTCA-CTGCACTTACCACCA-3 ¶ (reverse) for FAS À1377 G>A, 5 ¶-ATAGCTG-GGGCTATGCGATT-3 ¶ (forward) and 5 ¶-CATTTGACTGGGCTGTCCAT-3 ¶ (reverse) for the FAS À670 A>G (18), 5 ¶-CAATGAAAATGAACACAT-TG-3 ¶ (forward) and 5 ¶-CCCACTTTAGAAATTAGATC-3 ¶ (reverse) for FASLG À844 C>T, and 5 ¶-GCAGTTCAGACCTACATGATTAGGAT-3 ¶ (forward) and 5 ¶-CCAGATACAGACCTGTTAAATGGGC-3 ¶ for FASLG IVS2nt À124 A>G (28). The amplified PCR products were 122, 193, 85, and 230 bp for À1377 G>A, À670 A>G, À844 C>T, and IVS2nt À124 A>G polymorphisms, respectively.…”

Section: Methodsmentioning

confidence: 99%

Polymorphisms of FAS and FAS Ligand Genes Involved in the Death Pathway and Risk and Progression of Squamous Cell Carcinoma of the Head and Neck

Zhang¹,

Wang²,

Sturgis³

et al. 2006

Clinical Cancer Research

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Purpose: Alteration of the FAS/FAS ligand (FASLG) pathway regulating cell death may lead to cancer development, but the effects of functional promoter polymorphisms of the FAS and FASLG genes on risk of squamous cell carcinoma of the head and neck (SCCHN) are unknown. Design: We genotyped the FAS À1377 G>A, FAS À670 A>G, FASLG À844 C>T, and FASLG IVS2nt À124 A>G polymorphisms in 721case patients with SCCHN and 1,234 cancer-free nonĤ ispanic White control subjects frequency-matched by age and sex. Multivariate logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Compared with the FAS À1377 GG and À670 AA genotypes, the FAS À1377 AA and À670 (GG + AG) genotypes were associated with an increased risk of SCCHN (OR, 2.23; 95% CI, 1.07-4.64 and OR, 1.24; 95% CI, 1.01-1.52, respectively), whereas no risk of SCCHN was associated with any of the FASLG genotypes. When we used the combined FAS À1377 (GG + AG)/ À670 AA genotypes as the reference, we found that the individuals carrying the FAS À1377 AA/ À670 (GG + AG) had the highest risk (OR, 2.69; 95% CI, 1.24-5.83), whereas individuals carrying genotypes other than FAS À1377 (GG + AG)/À670 AA had a higher risk of SCCHN (OR, 1.24; 95% CI, 1.01-1.52). Furthermore, the elevated risk was particularly evident for pharyngeal cancer with the larger tumors without regional lymph metastasis (OR, 1.77; 95% CI, 1.07-2.94). Conclusions:The FAS (but not FASLG) polymorphisms seem to contribute to risk of developing SCCHN, particularly the pharyngeal cancer in non^HispanicWhites. However, potential selection bias warrants future population-based studies to verify the findings.

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Fas ligand gene polymorphisms are not associated with Hashimoto’s thyroiditis and Graves’ disease

Cited by 22 publications

References 20 publications

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma

Polymorphisms of FAS and FAS Ligand Genes Involved in the Death Pathway and Risk and Progression of Squamous Cell Carcinoma of the Head and Neck

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