A Dedicated Promoter Drives Constitutive Expression of the Cell-Autonomous Immune Resistance GTPase, Irga6 (IIGP1) in Mouse Liver

Background: In general, immune effector molecules are induced by infection. Methodology and Principal Findings: However, strong constitutive expression of the cell-autonomous resistance GTPase, Irga6 (IIGP1), was found in mouse liver, contrasting with previous evidence that expression of this protein is exclusively dependent on induction by IFNc. Constitutive and IFNc-inducible expression of Irga6 in the liver were shown to be dependent on transcription initiated from two independent untranslated 59 exons, which splice alternatively into the long exon encoding the full-length protein sequence. Irga6 is expressed constitutively in freshly isolated hepatocytes and is competent in these cells to accumulate on the parasitophorous vacuole membrane of infecting Toxoplasma gondii tachyzoites. Conclusions and Significance: The role of constitutive hepatocyte expression of Irga6 in resistance to parasites invading from the gut via the hepatic portal system is discussed

HindIII(+/-) polymorphism of the Y chromosome, blood pressure, and serum lipids: no evidence of association in three white populations.

BACKGROUND: Male sex is associated with elevated levels of cardiovascular risk factors, including higher blood pressure (BP). Genetic variants on the Y chromosome may contribute to explain the sexual dimorphism in cardiovascular diseases. Among them, the HindIII(+/-) polymorphism of the male-specific region of the Y chromosome has been associated with BP and serum cholesterol levels, with conflicting results. We evaluated the association between the HindIII(+/-) polymorphism, prevalence of hypertension, BP, and serum lipid levels in a large sample of white men and the previously reported epistatic interaction between HindIII(+/-) and the -344C/T polymorphism of the aldosterone synthase gene (CYP11B2) on BP. METHODS: From three European populations (UK n = 422; Belgium n = 313; Italy n = 1248) 1983 white men were phenotyped for BP and serum lipids and genotyped for HindIII(+/-) site and for -344C/T polymorphism in the promoter of CYP11B2 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A higher frequency of the HindIII (+) was found in Italians (63%) as compared to both British (31%) and Belgians (28%) (P < .0001). We found no evidence of association of the HindIII(+/-) site with prevalence of hypertension, BP, and serum lipids in any of the three European populations examined and in the entire sample. Finally, we did not observe any interaction between the HindIII(+/-) polymorphism and the -344C/T variant of CYP11B2 on BP. CONCLUSIONS: Our data do not support the hypothesis that the HindIII(+/-) site of the Y chromosome is a marker of cardiovascular risk in white men, highlighting the need for replication in genetic association studie

Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels. Cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study

To study the interaction between the C(-344)T polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone.Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy.Medical centre of the Olivetti factories.In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis.Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism.In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 +/- 0.6, versus CC: -0.4 +/- 1.5 mmHg, P= 0.04).Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation