Association between Hepatitis C Virus Viremia and the rs12979860, rs2228145 and rs1800795 SNP (CT/AC/GG) Genotype in Saudi Kidney Transplant Recipients.

BACKGROUND: Hepatitis C virus (HCV) is a major health problem, particularly in high-risk groups such as kidney transplant recipients, where it can adversely affect graft survival and increase the relative risk for mortality. Recently, the role of genetic variation among HCV patients in determining the outcome of infections has been under investigation. OBJECTIVE: To investigate the association of single-nucleotide polymorphisms (SNPs) rs12979860 (located within the interleukin-28B locus), rs2228145 (interleukin-6 receptor) and rs1800795 (interleukin-6 promoter) with HCV viremia in renal transplant patients. MATERIALS AND METHODS: In this analytical cross-sectional study, 149 kidney transplant recipients, 82 males (median age: 41 years) and 67 females (median age: 45 years), were screened for HCV RNA in blood using real-time polymerase chain reaction and genotyped by sequencing (rs12979860) and restriction fragment length polymorphism (rs2228145 and rs1800795). RESULTS: HCV RNA was detected in 17 (11.41%) of the 149 patients. There was no statistically significant association between the studied SNPs and HCV viremia. However, a combination of the CT/AC/GG genotype was significantly associated with HCV viremia (odds ratio: 5.4). The genotype AA of rs2228145 in the IL-6 receptor was associated with viremia levels of >105 copies/ml (odds ratio: 5.96). CONCLUSION: To the best of the authors' knowledge, this is the first study that has shown that the CT/AC/GG genotype has an impact on HCV viremia in kidney transplant patients. Therefore, such SNP genotypes may potentially be used to identify transplant patients at risk of HCV infection.

New sources for insulin-producing cells.

Cellular replacement offers the potential of a `cure` for type 1 diabetes mellitus. Shortage of suitable donors limits widespread implementation of this approach. Recent research has been focused on potential new sources of beta-cells including embryonic and adult stem cells, and other organs cells. The contribution of beta-cell replication to new islet formation, in addition to the potential for transdifferentiation of pancreatic acini and ductal cells in adult human pancreas is not clear. The existence of true stem cells within pancreas remains contentious issue. In this review, we summarized the possible sources of new insulin-secreting cells.

Pluripotency-associated stem cell marker expression in proliferative cell cultures derived from adult human pancreas.

The source of new ß-cells in adult human pancreas remains incompletely elucidated with recent studies on rodents providing evidence for neogenesis from progenitor cells in addition to self-replication. The aim of this study was to investigate the expression of pluripotency-associated stem cell markers in proliferative cultures derived from adult human pancreas. Human pancreatic tissue was obtained from deceased donors following ethical approval and relative consent. Islet-enriched fraction was separated from the retrieved organ by digestion and density gradient centrifugation. Dissociated cells were seeded in adherent culture forming proliferative 'islet survivor cells' (ISCs). These were characterised at fifth passage by RT-PCR, immunofluorescence staining, FACS, western blot and transfection studies with an OCT4 promoter-driven reporter. Nuclear expression of the pluripotency-associated stem cell marker complex OCT4/SOX2/NANOG was confirmed in ISCs. The phenotype constituted ∼8% of the overall population. OCT4 biosynthesis was confirmed by western blot and activation of an exogenous OCT4 promoter. Co-expression of pluripotency-associated markers has been confirmed in proliferative primary cells derived from adult human pancreas. Further studies are required to elucidate whether these cells possess functional stem cell characteristics and assess potential for differentiation into pancreatic cell lineages including new ß-cells.