Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients

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• 作者：Vinod D. Umare^a ; Vandana D. Pradhan^a ; Anjali G. Rajadhyaksha^b ; Manisha M. Patwardhan^a ; Kanjaksha Ghosh^a ; Anita H. Nadkarni^a ; ^{anitahnadkarni@yahoo.com}
• 关键词：Cytokines ; TNF-α ; LTα ; Indian SLE
• 刊名：Human Immunology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：78
• 期：2
• 页码：201-208
• 全文大小：809 K
• 卷排序：78

文摘

The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (−308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α −308A (OR 0;= 0;2.3, p 0;= 0;0.0001, Pc 0;= 0;0.0003) and LTα +252G (OR 0;= 0;2.1, p 0;< 0;0.0001, Pc 0;< 0;0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR 0;= 0;12.2, p 0;= 0;0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles. TNF-α −308G/A 0;+ 0;A/A genotypes (p 0;< 0;0.01) and LTα +252 A/G 0;+ 0;G/G genotypes (p 0;< 0;0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with −308G/A 0;+ 0;A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR 0;= 0;3.9, p 0;= 0;0.0014, Pc 0;= 0;0.0098) and anti-Sm antibodies (OR 0;= 0;4.1, p 0;= 0;0.0002, Pc 0;= 0;0.0014). The present study suggests TNF-α −308A and LTα +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-α and LTα and concomitant discrete clinical features among Indian SLE patients.