title: Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients.
abstract: 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=2.3, p=0.0001, Pc=0.0003) and LTα +252G (OR=2.1, p<0.0001, Pc<0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR=12.2, p=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+A/A genotypes (p<0.01) and LTα +252 A/G+G/G genotypes (p<0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with -308G/A+A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR=3.9, p=0.0014, Pc=0.0098) and anti-Sm antibodies (OR=4.1, p=0.0002, Pc=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.
authors.affiliation: National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai, Maharashtra 400012, India.
authors.forename: Vinod D
authors.initials: VD
authors.lastname: Umare
authors.affiliation: National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai, Maharashtra 400012, India.
authors.forename: Vandana D
authors.initials: VD
authors.lastname: Pradhan
authors.affiliation: Department of Rheumatology, Seth G.S. Medical College and King Edward Memorial Hospital, Parel, Mumbai, Maharashtra 400012, India.
authors.forename: Anjali G
authors.initials: AG
authors.lastname: Rajadhyaksha
authors.affiliation: National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai, Maharashtra 400012, India.
authors.forename: Manisha M
authors.initials: MM
authors.lastname: Patwardhan
authors.affiliation: National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai, Maharashtra 400012, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai, Maharashtra 400012, India. Electronic address: anitahnadkarni@yahoo.com.
authors.forename: Anita H
authors.initials: AH
authors.lastname: Nadkarni
mesh_terms: D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokines; Indian SLE; LTα; TNF-α