Association of Cytokine Gene Polymorphism with Susceptibility and Clinical Types of Leprosy

Background: Both pro- and anti-inflammatory cytokines are implicated in development and prognosis of leprosy so the genetic regulation of such cytokines could play an important role. Objective:. This study was planned for testing the association of cytokine gene polymorphisms with susceptibility and clinical types of leprosy among Egyptian cases. Subjects: This study included 47 cases (29 men, 18 females, mean age = 46.3 years) with leprosy in addition to 98 healthy unrelated controls (52 males, 46 females, mean age = 44.9 years). Cases were recruited from Leprosy Clinics, Delta region of Egypt. Cases were classified into paucibacillary (PB) (n = 17; 10 males, 7 females; mean age 42.6 years) and multibacillary (MB) (n = 29; 19 males, 10 females; mean age 43.9 years). Methods: For all cases and controls, DNA was extracted and amplified using polymerase chain reaction with sequence specific primers (PCR-SSP) for detection of single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes, TNF- - 308 (G/A), IL-10-1082(G/A), IL-6-174(G/C) as well as IL-1RaVNTR in intron 2 of the gene. Results: Compared to controls, all cases have shown increased frequency of homozygous genotypes : IL-10-1082 (GG) (Odds ratio 6.6, P <0.05), homozygous TNF- -308 (GG) (Odds ratio =3.23), and homozygous IL-1Ra (11) (Odds ratio = 3.6, P<0.05) with increased frequency of IL10 G and ILRa 1 alleles (P<0.05). BP subgroup showed increased frequency of homozygous IL- 10-1082 (GG) (Odds ratio = 18.6, P<0.05) with increased frequency of IL10 G allele (P<0.05). On the other hand, MB subgroup showed increased frequency of homozygous TNF- -308 (GG) (Odds ratio = 5.84, P<0.05) and homozygous IL-1Ra (11) (Odds ratio = 4, P<0.05) with increased frequency of IL-1Ra 1 allele (P<0.05). There is predominance for heterozygous IL-6-174 (G/C) polymorphism in all studies patient subgroups as well as controls with no significant difference among them. Conclusion: Genetic polymorphisms related to TNF- -308 and IL-10-1082 and IL-1Ra may be used as genetic markers for susceptibility and clinical outcome of leprosy among Egyptian cases from the Nile Delta. Abbreviations: TNF; tumor necrosis factor, IL; interleukine, IL-1Ra; IL-1 receptor antagonist, PCR; polymerase chain reaction, SNP; single nucleotide polymorphism, VNTR; variable number tandem repeat. Key words: Leprosy, Cytokines, Gene polymorphism, Egypt