Presentation: Association and Expression Study of PRKCH Gene in a French Caucasian Population with Rheumatoid Arthritis (2007)

1065 Association and Expression Study of PRKCH Gene in a French Caucasian Population with Rheumatoid Arthritis

Purpose. PRKCH gene, which encodes the η isozyme of protein kinase C (PKCη), is a good functional candidate for susceptibility to Rheumatoid Arthritis (RA) because this auto-immune disease is apparently caused by autoreactive T cells and PKC plays an important role in signal transduction controlling T cell activation. A previous study has shown that multiple single nucleotide polymorphisms (SNPs) located in 3 distinct linkage disequilibrium blocks were significantly associated with RA in a case-control Japanese population. Further, the PRKCH gene is expressed at high levels in resting T cells and this expression is down-regulated by immune responses suggesting that PKCη is involved in signalling pathways to T cells. The aim of this study was to test the PRKCH gene association with or linkage to RA in a family-based study from the French Caucasian population. Moreover, the level of expression of PRKCH messenger RNA (mRNA) between patients and controls and the correlation between the genotype and level of expression were studied.
Methods. 100 French Caucasian RA Trio families (one patient and both parents) were genotyped for +8134C/T, rs767755, rs912620 and rs959728 SNPs by PCR-RFLP and TaqMan®. Association and linkage were analysed using the Transmission Disequilibrium Test, the frequency comparison of the transmitted and un-transmitted alleles and the Genotype Relative Risk. Relative quantification of PRKCH mRNA expression was performed from whole blood in 24 RA unrelated patients and 16 controls by Real-Time PCR. The expression level of the PRKCH transcript was quantified using the treshold cycle (Ct) method. The correlation of the level of expression and the genotype of 24 RA patients was assessed by the Kruskal-Wallis ANOVA Test.
Results. There is no significant association or linkage between three SNPs (+8134C/T, rs912620 and rs959728) and RA (p>0.05). The SNP rs767755 was not analyzed because of a Hardy-Weinberg disequilibrium in the group constituted by non-transmitted parental alleles from RA trio families. The PRKCH messenger RNA was expressed at higher level in controls than in RA patients. We did not observed a significant correlation between the genotypes of the +8134C/T, rs912620 and rs959728 SNPs and the level of expression in RA patients (p>0.05).
Conclusions. This study provides evidence that the PRKCH gene is not a RA susceptibility genetic factor in the French Caucasian population. However, the down-regulation of the expression of PRKCH in RA patients compared to the controls suggests that PKCη could be involved in T cells dysregulation in RA.

 V.H. Teixeira, None.