The FAS−670 polymorphism influences susceptibility to multiple sclerosis

Kalkers, Nynke F.; Crusius, J. Bart A.; Winsen, L.M.L. van; Barkhof, Frederik; Jongen, P.J.H.; Peña, A. S.; Polman, Chris H.; Uitdehaag, Bernard M. J.

doi:10.1016/s0165-5728(02)00163-7

Cited by 33 publications

(23 citation statements)

References 28 publications

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“…41 Therefore, this SNP may affect the level of Fas gene transcription and may induce apoptosis, consequently increasing the risk of LA. The Fas A-670G polymorphism has been reported to be associated with several autoimmune diseases and inflammatory disorders, [41][42][43] which may involve a mechanism similar to LA. The frequency of the AA genotype of Fas -670 in 829 HIV-1-infected Thais was 22.1%, which is similar to the percentages in Europeans and Japanese but is markedly higher than that in Africans.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

Likanonsakul

Rattanatham

Feangvad

et al. 2013

AIDS Research and Human Retroviruses

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The present study aimed to evaluate the role of genetic polymorphisms in the emergence of lipoatrophy or lipodystrophy in HIV-infected patients with antiretroviral therapy (ART) in Thailand. Position 455 upstream of the Apolipoprotein C3 gene (ApoC3 T-455C, rs2854116), codon 64 of the Beta3 adrenergic receptor gene (ARb3 Tcod64C, rs4994), and position 670 upstream of the Fas gene (Fas A-670G, rs1800682) were genotyped in 829 HIV-infected Thai patients who had started ART. Crude and adjusted incidence rate ratios (IRR) were calculated using Poisson regression. The serum levels of cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also analyzed. Multivariate analysis revealed an association between the Fas -670AA genotype, but not the ApoC3 -455 or ARb3 cod64 genotypes, with the incidence of lipoatrophy after adjusting for gender and stavudine (d4T)-containing regimens (IRR = 1.72, 95% CI = 1.20-2.45, p = 0.003). However, ApoC3 -455C homozygous patients showed elevated serum levels of triglycerides, while this genotype did not affect serum total cholesterol, HDL, or LDL levels in patients with lipoatrophy or lipodystrophy. In contrast, the ARb3 cod64 genotype did not show any significant association with the serum levels of cholesterol, triglycerides, HDL, or LDL. In conclusion, Fas -670AA affected the incidence of lipoatrophy in HIV-1-infected Thai patients, while the ApoC3 -455C allele affected the serum levels of triglycerides. These results confirmed the role of genetics in the development of ART-related metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

Likanonsakul

Rattanatham

Feangvad

et al. 2013

AIDS Research and Human Retroviruses

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“…The FAS -670A>G polymorphism has been linked to susceptibility to autoimmune diseases such as SLE and multiple sclerosis (Kanemitsu et al, 2002;van Veen et al, 2002;Agarwal et al, 2007). However, another group of studies in different populations found no such association (Niino et al, 2002;Arasteh et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…The FAS -670A allele was associated with susceptibility to systemic lupus erythematosus (SLE) in a Japanese population (Kanemitsu et al, 2002). However, contradictory results between populations have been found in several autoimmune diseases (Kanemitsu et al, 2002;Niino et al, 2002;van Veen et al, 2002;Hiraide et al, 2005;Agarwal et al, 2007;Arasteh et al, 2010). A study in Caucasians found no association of the polymorphism with pSS susceptibility; however, the authors did not assess the possible influence of the FAS -670A>G polymorphism on sFas levels (Mullighan et al, 2004).…”

Section: Introductionmentioning

confidence: 98%

FAS -670A>G promoter polymorphism is associated with soluble Fas levels in primary Sjögren’s syndrome

et al. 2014

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ABSTRACT. Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Soluble Fas receptor (sFas) has been suggested as a Fas-mediated apoptosis blocker that could impair clonal deletion in infiltrated autoreactive cells. The FAS -670A>G promoter polymorphism has been studied in pSS. However, a relationship between FAS -670A>G promoter polymorphism and sFas levels in pSS had not been found. We examined this relationship in 77 Mexican pSS patients and 84 healthy subjects were included. Genotypes were identified by PCR-RFLP, and Fas soluble levels were quantified by ELISA. No significant differences between allele and genotype frequencies were found between these two groups. The sFas levels in the serum of pSS patients were significantly higher than in controls (9961 vs 8840 pg/mL, respectively). In addition, AA genotype carriers had significantly higher levels of sFas than GG carriers (pSS: 10,763 and 9422 pg/mL; controls: 9712 and 8305 pg/mL, respectively). An additive model analysis between genotypes (AG+GG vs AA) in both groups, demonstrated a significant association between carriers of the A allele and high sFas levels. In conclusion, carrying the double dose of A allele of FAS -670A>G polymorphism is associated with high levels of sFas in pSS, but it is not a susceptibility marker for pSS.

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“…Moreover, oral contraceptives have been shown to be associated with increased risk for CD [37] . It has been proposed that epigenetic factors play an important role in the pathogenesis of IBD [38] , and that sex effects are mediated by sexual hormones, which have an effect on gene expression and consequently could lead to differential expression of disease susceptibility genes in males and females. According to our findings, it appears that Fas/Apo1 gene polymorphisms decrease susceptibility to CD and UC in females in the Tunisian population.…”

Section: Discussionmentioning

confidence: 99%

Association of Fas/Apo1 gene promoter (-670 A/G) polymorphism in Tunisian patients with IBD

Aleya¹,

Sfar²,

Mouelhi³

et al. 2009

WJG

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AIM:To detect a possible association between the polymorphism of the (-670 A/G) Fas/Apo1 gene promoter and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. METHODS:The (-670 A/G) Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: Significantly lower frequencies of the Fas -670A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of (-670 A/G) Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls (P corrected = 0.004 in CD patients and P corrected = 0.02 in UC patients, respectively). Analysis also showed a statistically significant association between genotype AA of the (-670 A/G) polymorphism and the ileum localization of the lesions (P corrected = 0.048) and between genotype GG and the colon localization (P corrected = 0.009). The analysis of inflammatory bowel disease patients according to clinical behavior revealed no difference. CONCLUSION:Fas-670 polymorphism was associated with the development of CD and UC in the Tunisian population.

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The FAS−670 polymorphism influences susceptibility to multiple sclerosis

Cited by 33 publications

References 28 publications

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

FAS -670A>G promoter polymorphism is associated with soluble Fas levels in primary Sjögren’s syndrome

Association of Fas/Apo1 gene promoter (-670 A/G) polymorphism in Tunisian patients with IBD

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