Identification and functional characterization of a highly polymorphic region in the human TRAIL promoter in multiple sclerosis

Weber, Alexandra; Wandinger, Klaus‐Peter; Mueller, Wolf; Aktaş, Orhan; Wengert, Oliver; Grundström, Eva; Ehrlich, Stefan; Windemuth, Christine; Wienker, Thomas F.; Brück, Wolfgang; Zipp, Frauke

doi:10.1016/j.jneuroim.2003.12.014

Cited by 27 publications

(20 citation statements)

References 39 publications

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“…Isolation and characterization of the 5'-upstream region of the gene was carried out and 4 SNPs was reported in this region, using human colorectal cancer cell lines [9] and four SNPs were reported in 3'UTR of TRAIL gene [10,11]. One SNP in the 3'UTR [12] and four SNPs in the polymorphic region [13] reported in multiple sclerosis. Moreover, SNPs of TRAIL have been reported in fatty liver disease [14], breast cancer [15], sporadic breast tumor [5] and prostate cancer [16].…”

Section: Introductionmentioning

confidence: 99%

sTRAIL Serum Levels and TRAIL 1595 Genotypes: Associations with Progress and Prognosis of Colorectal Carcinoma

Yaylım¹,

Ozkan²,

Turan³

et al. 2012

JCT

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Programmed cell death called apoptosis, plays an important role in the development and maintenance of tissue homeostasis and abnormalities in apoptotic function have been known as important events in the pathogenesis of many cancer types, such as colorectal cancer. It has been shown that both the membrane-bound TRAIL and sTRAIL can induce apoptosis in several tumor types by activating death receptors. Our study was to investigate the existence of TRAIL 1595 C/T SNP in colorectal cancer patients and possible effects of this substitution on serum levels of sTRAIL. In the present study, TRAIL 1595 C/T polymorphism was genotyped in 76 patients with colorectal cancer and 98 healthy subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There were no significant differences in the distribution of TRAIL 1595 C/T genotypes and frequencies of the alleles between colorectal cancer patients and controls. The increased frequency of TRAIL 1595 homozygotes genotypes in patients who had advanced tumour stage was statistically significant (p = 0.0082). Serum sTRAIL levels in the colorectal patients with CT genotype were lower than those of patients with early tumor stage (p = 0.028). The decreased sTRAIL levels were observed in the patients with distant metastasis and CT genotype (p = 0.023).Our findings have suggested that TRAIL 1595 C/T genotypes and sTRAIL levels might be associated with the progression of colorectal cancer in Turkish population.

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Section: Introductionmentioning

confidence: 99%

sTRAIL Serum Levels and TRAIL 1595 Genotypes: Associations with Progress and Prognosis of Colorectal Carcinoma

Yaylım¹,

Ozkan²,

Turan³

et al. 2012

JCT

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“…No significant differences in the distribution of the genotypes were observed as to mean age at onset of the disease, disease progression (edSS increase per year), and gender ratio. the authors suggested that these SnPs in the trail promoter exert no impact on molecule expression, and are neither directly related to the increased risk of developing mS nor associated with a clinical course of this heterogeneous disease in German mS patients (90).…”

Section: Apolipoprotein E Gene (Apoe)mentioning

confidence: 99%

“…due to its implication in brain damage and the elevated expression in peripheral immune cells of mS patients, trail may play a central role in the pathology of this disease. a highly polymorphic region in the trail promoter with four SnPs within 11 base pairs was identified using single-strand conformation polymorphism analysis (90). the polymorphisms are located at positions -707 (c→t), -665 (t→c), -621 (c→t) and -597 (a→G) of the wild-type sequence.…”

Section: Apolipoprotein E Gene (Apoe)mentioning

confidence: 99%

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

Kallaur

Kaimen-Maciel²,

Morimoto³

et al. 2011

Int J Mol Med

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Abstract. multiple sclerosis (mS) is an autoimmune disease characterized by areas of inflammation, demyelination and axonal damage. the etiology of mS is multifactorial with an interaction between genetic, environmental and geographical factors. the objective of this study was to review the physiopathology and the genetic polymorphisms associated with the development and clinical course of mS. Studies carried out in populations worldwide showed that polymorphisms in the genes of the major histocompatibility complex (mHc) class ii and class iii have been associated with susceptibility, resistance and clinical forms of mS. considerable attention has been focused on studies evaluating disease-modifying effects in MS that identified seven genes of probable importance such as the Hla class ii, apoe, il-1ra, il-1β, tnf-α, tnf-β and ccr5 genes. However, the results described in the literature about genetic biomarkers in mS are not consistent in the worldwide population. the detection of a single nucleotide polymorphism involved in the etiology and physiopathology of MS is very difficult and, it is likely that, several genetic polymorphisms are involved, each with a small contribution to the susceptibility or resistance to mS. taken together the results show the need for continued research in genetically heterogeneous populations to identify new biomarkers associated with mS that could be used as prognostic markers or as therapeutic targets to modulate the autoimmune response in mS patients. this information may contribute to a better understanding of the physiopathology and treatment of mS, with the possibility of developing different therapeutic strategies according to the genetic profile of each individual.

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“…Polymorphism of CCR2, IL-10 receptor α, and Fas-L may confer protective effects for MS; and polymorphism of CCR5, IL-10, IL-4 receptor α, IL-2 receptor ß, IFN-γ, vitamin D, and estrogen receptor confer risk to MS (1). However, genetic studies carried out on MS patients from different worldwide populations have shown conflicting results (16)(17)(18)(19)(20)(21).…”

Section: Ccr5-δ32 Genetic Polymorphism Associated With Benign Clinicamentioning

confidence: 99%

CCR5-Δ32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis

Kaimen-Maciel

Reiche²,

Souza³

et al. 2007

Int J Mol Med

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Abstract. The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). This research was carried out to investigate the association between the CCR5-Δ32 deletion in 124 patients with MS from Southern Brazil. Ninety-eight (79.0%) patients presented with relapsingremitting MS (RR-MS), 17 (13.7%) secondary progressive MS (SP-MS), 8 (6.5%) primary progressive MS (PP-MS) and one (0.8%) clinically isolated syndrome (CIS). The control group consisted of 127 healthy blood donors from the same geographic region. The disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS). Genomic DNA was extracted from peripheral blood cells and the genetic polymorphism was evaluated by polymerase chain reaction. Of the MS patients, 85 (68.5%) were females (p=0.0093). The CCR5-Δ32 frequency among the controls was 5.5%, and did not differ from that observed among the MS patients (4.8%) (p=0.7337). The mean (±SD) age at disease onset among the carriers and non-carriers of the CCR5-Δ32 allele was 31.7 (±11.1) and 36.6 (±12.0) years, respectively (p=0.1312). The duration (±SD) of the disease was 11.2 (±12.9) and 7.7 (± 5.6) years among the CCR5-Δ32 heterozygous, and CCR5 wild type, respectively (p=0.396). The mean (±SD) EDSS among the MS patients carriers and non-carriers of the CCR5-Δ32 allele was 2.4±1.2 and 2.67±2.2, respectively (p=0.9796). The MRI findings in MS patients with the CCR5-Δ32 genotype exhibited lower positive gadolinium enhancing-imaging (p=0.0013) and lower brain atrophy (p=0.1333) than MS patients with the CCR5 wild-type genotype. Despite that the differences were not significant, the results suggested that the disease onset and progression to disability may be prolonged in MS carriers of CCR5-Δ32, and CCR5-Δ32 could be considered a favorable prognostic biomarker of MS. Further studies comprising larger numbers of individuals carrying non-wild-type haplotypes are needed to determine CCR5-Δ32 involvement in the specific process of MS pathology and pathogenesis.

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Identification and functional characterization of a highly polymorphic region in the human TRAIL promoter in multiple sclerosis

Cited by 27 publications

References 39 publications

sTRAIL Serum Levels and TRAIL 1595 Genotypes: Associations with Progress and Prognosis of Colorectal Carcinoma

sTRAIL Serum Levels and TRAIL 1595 Genotypes: Associations with Progress and Prognosis of Colorectal Carcinoma

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

CCR5-Δ32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis

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