The etiology of bipolar disorder (BPAD) is still unknown, but family, twin, and adoption studies strongly suggest the involvement of genetic risk factors. Linkage studies have revealed a number of loci to be linked with BPAD. Of those, several investigators confirmed 18p11 as one of the susceptibility loci for BPAD. Thus, chromosome 18p11 is one of the targets of the genetic association study of BPAD. The aim of our study was to investigate whether the tandem repeat polymorphism in D18S452 microsatellite marker at locus 18p11.2 is a risk factor for the development of BPAD in Kashmiri population. The repeat polymorphism in D18S452 was evaluated in 74 patients with BPAD and 74 control (age, sex and region matched) individuals. The repeat polymorphism was evaluated by PCR analysis of DNA obtained from the blood of the subjects. We observed that the tandem repeat (300bp*) allele frequency was found to be 1.35 % in the controls and 8.108% in cases. The tandem repeat (250bp*) allele frequency was found to be in 91.89% in cases and 98.65% in controls. The 252bp/252bp genotype was found to be present in 89.18% of the cases and 98.64% of the controls, the 300bp/300bp genotype in 5.40% of cases and 1.35% of controls and the 252bp/300bp variant in 5.40% of the cases and none among the controls. It was observed that although the proportion of patients homozygous for the tandem repeat (300bp/300bp) was higher in cases than in controls, the difference was not statistically significant when using 252bp/252bp genotype as a reference (OR= 4.4242; 95% CI, 0.4822-40.5924); P = 0.1529). However, it was observed that the frequency of the heterozygous genotype (252bp/300bp) when compared with 252bp/252bp showed statistical significance (OR=8.0603; 95% CI, 1.1112-58.4646; P = 0.0383).
Chromosome 18 harbors many candidate genes that are involved in the pathophysiology of BPAD. It may be possible that this marker is directly or indirectly involved in the regulation of neighboring genes. It is also possible that this locus may be in linkage disequilibrium with other genes. Although, this is the first study reporting the association of the marker D18S452 in heterozygous condition (252bp/300bp) with BPAD. Yet, it would be too early to associate this genotype with the predisposition to BPAD. Therefore, further studies with larger sample size should be carried to validate the result, taking into account the various disease phenotypes, endophenotypes and environmental conditions
