Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174 GC polymorphism

Abstract

Natural killer group 2D (NKG2D), as an activating receptor, plays pivotal role in viral infectious diseases. Several single nucleotide polymorphisms (SNPs) in the NKG2D gene have characterized that the rs1049174G/ C SNP of NKG2D is in the spotlight of notice because of its role in activating of human T cells. This study aimed to investigate rs1049174G/C genetic polymorphism in Chronic Hepatitis C (CHC) patients. The study compromised 107 CHC patients with genotype 1a and 1b. All recruited patients were under treatment with Peginterferon Alfa-2a/Ribavirin according to standard protocol. After completing treatment, 67 patients showed sustained virologic response (SVR) and the rest of patients did not respond to the treatment and considered as non-responder (NR). Genotyping of NKG2D rs1049174G/C SNP was performed using PCR-RFLP method in SVR and NR patients. The NKG2D rs1049174 genotypes frequency for GG, GC and CC were 45, 41 and 14 % respectively. Genotypes distribution were significantly different between SVR and NR groups (p = 0.005). So that the patients with the homozygous GG genotype demonstrated a higher response to Peginterferon Alfa-2a/Ribavirin therapy against HCV infection (OR = 6.0, 95 %CI 1.71-21.08, p = 0.005). In conclusion, the rs1049174 GG genotype of NKG2D receptor is an effective factor in successfully treatment of CHC patients by Peginterferon Alfa-2a/ Ribavirin.

NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

“…NKG2D gene variability can be regarded as a marker for virus treatment outcome. In Iranian patients suffering from chronic HCV infection, an association with treatment outcome and NKG2D polymorphism was observed [68]. The rs1049174 G allele or GG genotype were predictive factors of sustained virologic response after Peginterferon Alfa-2a/Ribavirin treatment.…”

“…Carrying the HNK1/HNK1 and HNK1/LNK1 haplotypes is associated with significantly increased NKG2D protein surface expression on NK cells and reduced overall cancer risk, compared to the LNK1/LNK1 haplotype [57,89]. CC homozygosity associated with higher risk of EBV-infected nasopharyngeal carcinoma in Vietnamese patients [67] GG genotype in chronic hepatitis C Iranian patients demonstrated higher response to Peginterferon Alfa-2a/Ribavirin therapy against HCV infection [68] No association between Caucasian alleles and CMV infection in the first year after kidney transplantation [69] Donor GG genotype associated with improved overall survival and transplant related mortality in Japanese patients with standard risk disease after HLA-fully matched unrelated BM transplantation; no impact on disease relapse or development of aGvHD, cGvHD [70] C allele associated with decreased risk of recurrent miscarriages among Iranian women [71] rs2255336 (A, C > G, T)…”

“…Some alleles can be used as markers of severe clinical presentation of the disease [65,79,80]. KLRK1 gene polymorphism may represent a potential biomarker for prediction of treatment outcome in patients with cancers, autoimmune diseases or virus induced diseases [62,64,68,70,83]. Modern approaches such as genome-wide association studies expand genotyping in immunogenetics research.…”

The Donor Major Histocompatibility Complex Class I Chain-Related Molecule A Allele rs2596538 G Predicts Cytomegalovirus Viremia in Kidney Transplant Recipients

“…The NKG2D rs1049174 G/C SNP was performed by PCR-RFLP as previously described by Asadi-Saghandi et al with the following forward and reverse primers: 5′-TTAAGGCTGGAGAATAATGC-3′ and 5′-TCAGTGAAGGAAGAGAAGG-3′ ( 45 ).…”