Academic journal article Indian Journal of Psychiatry

Analysis of the Role of Human Leukocyte Antigen Class-I Genes to Understand the Etiopathology of Schizophrenia

Academic journal article Indian Journal of Psychiatry

Analysis of the Role of Human Leukocyte Antigen Class-I Genes to Understand the Etiopathology of Schizophrenia

Article excerpt

Byline: Bisu. Singh, Sikta. Banerjee, Nirmal. Bera, Chitta. Nayak, Tapas. Chaudhuri

Background: Schizophrenia is the paradigmatic illness of psychiatry. The involvement of immunological and immunopathological mechanisms in the etiopathogenesis of schizophrenia has been a matter of research, with recently increasing effort. Aims: In this study, we investigated the incidence of human leukocyte antigen (HLA) Class I antigens to understand the role of HLA genes in schizophrenia. Materials and Methods: India born schizophrenic patients in and around Siliguri who attended outpatient department (OPD) of Department of Psychiatry, North Bengal Medical College and Hospital were considered for the present study. After the longitudinal follow up, 50 patients were enrolled for the study. The same number of age, sex and ethnically matched healthy subjects were considered as control. Low resolution polymerase chain reaction-sequence specific primer method was applied for typing the HLA antigens. Statistics: The phenotype frequencies were calculated by direct count. ?[sup]2 test was done to compare the frequency of each antigen among the patients and control group and it was followed by Fisher's exact test. Relative risk was estimated by using Haldane's method. Results: The result showed that some of the HLA antigens are associated with the schizophrenia and significant increase were observed for HLA AFNx0103 antigen along with the significant decrease for HLA AFNx0125, AFNx0131 and HLA BFNx0151. Conclusions: The study provides the evidence for the possible existence of susceptibility locus for schizophrenia within the HLA region. This preliminary observation may help to understand the etiological basis of this disorder and the study may further strengthen the HLA antigens as the marker for schizophrenia.

Introduction

Schizophrenia is a severely debilitating neuropsychiatric disorder characterized by "disturbances of thought, auditory hallucinations and multiple delusions".[sup] [1] It affects 1% of the worldwide population.[sup] [2] The essential biological pathology of schizophrenia ia partially understood till to date.[sup] [3] However, there is substantial evidence to indicate a major genetic component.[sup] [4],[5] Different chromosomes have been pinpointed as harbouring genes involved in the pathogenesis of schizophrenia.[sup] [6] A susceptibility locus has been identified on chromosome 6.[sup] [7],[8] Several researches have also found evidence for schizophrenia vulnerability genes on chromosome 6p close to the HLA genetic region by linkage analysis.[sup] [9] HLA and schizophrenia was first reviewed by Mc Guffin (1979),[sup] [10] who commented that the MHC was a logical place in which to search for genetic markers for schizophrenia because schizophrenia was similar to diseases for which HLA association had been established in that it was familial, had an imperfectly understood etiology, and had a postulated autoimmune pathogenesis.[sup] [11]

The first HLA association study of schizophrenia was reported by Cazzullo et al ., in 1974.[sup] [12] More than 60 association studies have been reported since then.[sup] [13] The details of past association studies is given in [Table 1].

Past association studies with various Class I and Class II alleles yielded inconsistent results[sup] [14] except HLA-AFNx019 (now subdivided into AFNx0123/AFNx0124).[sup] [15] In different ethnic population, associations have been found for HLA-A9,[sup] [16] HLA-A23,[sup] [17] HLA-AFNx0124,[sup] [18] HLA-AFNx011,[sup] [19] HLA-AFNx012, HLA-AFNx013, HLA-AFNx0111, HLA-BFNx0117, HLA-BFNx0127, HLA-BFNx018 and Cw 2,[sup] [20] HLA-AFNx013.[sup] [21] The reason for the inconsistencies include the diagnostic methods, particularly in early studies , are imprecise and vary greatly.[sup] [22] The majority of the previous association studies were carried out using serological typing techniques [microlymphocytotoxicity testing][sup] [23] , which have been found to be inaccurate, with 7-25% misassignment errors[sup] [24] compared with the DNA based techniques (polymerase chain reaction (PCR) and sequence specific oligonucleotide probes (SSOP). …

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