Chemokine and Chemokine Receptor Polymorphisms in Bipolar Disorder

OBJECTIVE: Bipolar disorder (BD) is a debilitating psychiatric disease with unknown etiology. Recent studies have shown inflammation as a potential contributing factor of BD pathogenesis. However, potential associations between chemokine and chemokine receptor polymorphisms and BD have been fundamentally understudied. To identify participation of chemokines in BD pathogenesis, we examined genetic variants of several chemokine and chemokine receptor genes. METHODS: The study population comprised 200 patients with BD and 195 age- and sex-matched healthy controls. Genotyping of monocyte chemotactic protein 1 (MCP-1) A2518G, CCR2 V64I, CCR5 Δ32, CCR5 A55029G, stromal cell-derived factor 1 (SDF-1) 3'A, and CXCR4 C138T polymorphisms was performed using polymerase chain reaction and restriction enzyme digestion. RESULTS: We found that CCR5-Δ32 II and CXCR4-C138T C+ genotype frequencies contributed to an increased risk for BD. However, no statistical significance could be obtained with these genotypes after Bonferroni correction. A significant asssociation was only found with MCP-1 GG and G+ genotypes, which were markedly more prevalent in patients with BD and these genotypes seemed to significantly increase the risk for BD even after Bonferroni correction. CONCLUSION: Our findings indicate an association between genetic variants of certain chemokine and chemokine receptor (especially MCP-1) genes and BD. The exact mechanisms by which these variants contribute to BD pathogenesis and their clinical implications need to be further investigated.

Increased complement consumption in musk-antibody-positive myasthenia gravis patients

To investigate the activation of different complement pathways in myasthenia gravis [MG] subtypes. Levels of complement breakdown products for different complement pathways were measured using ELISA in sera of acetylcholine receptor antibody [AChR-Ab]-positive [n = 21], muscle-specific receptor tyrosine kinase [MuSK]-Ab-positive [n = 23] and seronegative generalized MG patients [n = 21] and healthy controls [n = 22]. Levels of factor Bb [FBb], the breakdown product of factor B, and C4d, the breakdown product of C4, were measured to evaluate the activity of the alternative and classical complement pathways, respectively. Serum iC3b levels were analyzed to assess total complement activity. The results were expressed as OD values. MuSK-Ab-positive MG patients had a significantly higher mean concentration of serum FBb [0.638] than other MG subtypes [0.446 for AChR-Ab-positive, 0.537 for seronegative MG patients] and healthy controls [0.434] [p = 0.045]. Mean serum iC3b [1.549-1.780] and C4d [0.364-0.395] levels were comparable among the groups. Our results suggest that MuSK-Ab-positive MG patients might have a complement-activating serum factor and the alternative complement pathway might be involved in the pathogenesis of the disease