A case-control association of RANTES (-28C >G) and CCR5-Delta32 polymorphisms with Parkinson's disease in Indians.

Recent studies have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. Also, numerous lines of evidence have indicated that inflammatory processes are involved in the pathogenesis of Parkinson's disease (PD). We have examined whether single nucleotide polymorphisms at the genes encoding chemokines RANTES (-28 C > G), RANTES (-403 A > G) MCP-1 (-2518 A > G), and chemokine receptors CCR2 (+190 G > A) and CCR5 (-Δ32) were associated with sporadic PD risk in the Indian population. This pilot case-control association study included 97 PD patients and 100 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. There was no statistically significant difference in the genotype frequencies between the cases and controls for the MCP1 (-2518 A > G), RANTES (-403 A > G) and CCR2 (+190 G > A) polymorphisms. However, the results revealed a significant difference in the frequency of the heterozygous CG genotype for the RANTES (-28 C > G) polymorphism (OR = 0.49, p = 0.03) between the cases and controls. A negative association was demonstrated in the dominant model where, compared with the GG genotype, a higher frequency of the GC + CC genotype was observed in the controls. Also, a statistically significant higher frequency of the CCR5 heterozygous genotype WT/Δ32 in the controls was observed (OR = 0.31, p = 0.04). Combined genotype analysis revealed that the allele combination of G-A-G-C of CCR2 (+190G > A), MCP-1 (-2518 A/G), RANTES (-403 A/G) and RANTES (-28 C/G) respectively had a risk association with PD (OR = 6.18, p = 0.005).

Factors, mechanisms and implications of chromatin condensation and chromosomal structural maintenance through the cell cycle.

A series of well-orchestrated events help in the chromatin condensation and the formation of chromosomes. Apart from the formation of chromosomes, maintenance of their structure is important, especially for the cell division. The structural maintenance of chromosome (SMC) proteins, the non-SMC proteins and the SMC complexes are critical for the maintenance of chromosome structure. While condensins have roles for the DNA compaction, organization, and segregation, the cohesin functions in a cyclic manner through the cell cycle, as a "cohesin cycle." Specific mechanisms maintain the architecture of the centromere, the kinetochore and the telomeres which are in tandem with the cell cycle checkpoints. The presence of chromosomal territories and compactness differences through the length of the chromosomes might have implications on selective susceptibility of specific chromosomes for induced genotoxicity.