No evidence for PERV release by islet cells from German landrace pigs.

BACKGROUND: Islet cells from pig could be used as an alternative to the current treatment of diabetic patients. However, xenotransplantation from pig to humans may be associated with the risk of transmission of porcine endogenous retroviruses (PERVs) that are present in the genome of all pigs and infect human cells in vitro. Although transplantation of pig islet cells for treatment of diabetes may be not accompanied by immunosuppression that may facilitate virus survival, since islets will be used encapsulated, it is nevertheless of importance to study whether islet cells release PERVs able to infect human cells during co-incubation. MATERIAL/METHODS: Isolated islets from German landrace pigs were incubated with highly susceptible human 293 cells for one week. In order to prevent microchimerism 293 cells were made neomycin-resistant (293(neo+)), that allows the elimination of pig cells by a selection medium. The infection of 293(neo+ )target cells was analysed by PCR using PERV-specific primers up to fi ve weeks after co-cultivation. In addition, expression of viral mRNA in pig islet cells was studied by RT-PCR analysis, the expression of viral protein by FACS analysis. RESULTS: Despite the presence of numerous PERV proviruses in the genome of all pigs, no expression of PERV was observed in German landrace pig islet cells, neither as mRNA, nor as protein, nor as viral particles. CONCLUSIONS: Islet cells from German landrace pigs do not express PERVs and may therefore be used for breeding genetically modified pigs suitable for xenotransplantation and treatment of diabetes.

Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.

BACKGROUND: Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. METHODS: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. FINDINGS: Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7)). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. CONCLUSION: A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD.