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Is single nucleotide polymorphism of the FAS A-670G gene associated with systemic lupus erythematosus patients from South Indian tamils?
Manikandan Natesan1, Arunagirinathan Narasingam1, Ganesh Balasubramanian2
1 Department of Microbiology, Presidency College, Chennai, Tamil Nadu, India
2 Laboratory Division, ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India
|Date of Submission||17-Aug-2020|
|Date of Acceptance||13-Oct-2020|
Department of Microbiology, Presidency College, Chennai - 600 005, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this URL:|
Natesan M, Narasingam A, Balasubramanian G. Is single nucleotide polymorphism of the FAS A-670G gene associated with systemic lupus erythematosus patients from South Indian tamils?. Indian J Rheumatol [Epub ahead of print] [cited 2021 Feb 26]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=309611
Systemic lupus erythematosus (SLE) is a severe rheumatic disease that affects multiple tissues and organs. FAS/FASL pathway plays a critical role in apoptosis process; therefore, the apoptosis gene FAS is the candidate gene in SLE predisposition., Therefore, the aim of this present study was to investigate the association of apoptosis gene, FAS A-670G (rs1800682) polymorphism, with SLE susceptibility in South Indian Tamils.
A total of 83 SLE patients and 50 age-matched healthy subjects were included. The study was approved by the Ethical Committee of Madras Medical College and Hospital, Chennai, Tamil Nadu, and informed written consent was obtained from each participant. Blood samples were collected, and genomic DNA was extracted by a rapid, nonenzymatic method. The polymorphic site at nucleotide position-670 in the enhancer region of the FAS gene was amplified, and the genotypes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism method using the following primers: forward-5'CTACCTAAGAGCTATCTACCGTTC3' and reverse 5'GGCTGTCCATGTTGTGGCTGC3'. The amplified PCR product of FAS gene was digested with restriction enzyme BstN1 (New England Biolabs, MA, USA).
The 331 bp PCR amplicon copies were digested various fragments by the BstNI [Figure 1]. The AA, AG, and GG genotype frequencies of the FAS A-670G in SLE patients and controls were 28.9%, 56.62%, and 14.45% and 40%, 46%, and 14%, respectively. The A and G allele frequencies were 57% and 43% in SLE cases and 63% and 37% in controls. The frequency of the AA genotype of FAS A-670G polymorphism was lower in SLE patients (29%) as compared to controls (40%). However, the frequency of the AG genotype was higher in SLE patients (57%) compared with controls (46%) and the risk of SLE was 1.7-fold greater in individuals with AG genotype in comparison to AA genotype (odds ratio, 1.7 [95% confidence interval, 0.7–3.6]; P = 1.7). There were no differences between SLE patients (14.4%) and controls (14%) in the case of GG genotype (P = 0.5). The frequency of G allele was higher in the SLE group (42.7%) as compared to controls (37%).
|Figure 1: Restriction fragment length polymorphism of FAS A-670G gene polymorphism in SLE by BstNI. The FAS gene wild-type allele (a) has one restriction site that produces two fragments (233 and 98 bp). When the A allele is replaced by G, the 233 bp fragment is further cleaved into two fragments (189 and 44 bp) because the replacement creates a new BstNI restriction site|
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The results of this study found no significant association of FAS genotypes and alleles in SLE patients and controls. In contrast to the present study, a significant difference was observed in AA genotype frequency between Iranian SLE patients and controls in comparison to GG genotype, and the risk of SLE was 2.1-fold higher in subjects with AA genotype. Our study results were agreeing with the study by Lee et al., who had reported that the genotype distribution of the FAS promoter 670 did not differ between patients with SLE and control subjects. In another study, Lee et al. had reported that the FAS 670 A/G polymorphisms confer susceptibility to autoimmune rheumatic diseases and FAS 670G allele was negatively associated with SLE susceptibility.
In conclusion, association of FAS A-670G gene polymorphism does not appear to be a risk factor for SLE in Southern Indian Tamils. Further studies are needed to illuminate the role of FAS A-670G gene polymorphism in SLE susceptibility.
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Conflicts of interest
There are no conflicts of interest.
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