102T/C polymorphism of serotonin receptor type 2A gene is not associated with schizophrenia in either Chinese or British populations

Abstract

Several pieces of evidence implicate serotonin receptors in the aetiology of schizophrenia, and recently a number of studies have reported a genetic association between the 102T/C polymorphism of serotonin receptor type 2A gene and schizophrenia. Unfortunately a number of failures to replicate these positive associations in both Caucasian and Chinese populations have also been reported. We have examined the 102T/C polymorphism by PCR amplification and restriction analysis of DNA from: 202 schizophrenics and 202 controls from Shanghai; 112 schizophrenics and 224 parents from Chengdu, Cina; and 253 schizophrenics and 244 controls from the the UK. We find no evidence of association or transmission disequilibrium between the 102T/C polymorphism and schizophrenia in any of the groups we have examined. We conclude that either the original positive reports occurred by chance or any effect must be minimal, and urge caution in interpreting small positive results derived using data from different centres.

No evidence for an association between the 5‐hydroxytryptamine 5‐HT2a receptor gene and schizophrenia in Kuwaiti Arabs

“…However, their data did not substantiate the hypothesis that the effect of allele 2 was due to the parent of origin, as suggested by Kato et al. 17 In view of major theoretical and clinical implications of these reported associations between the 5‐HT 2a receptor gene and schizophrenia, several groups have tried to replicate the findings with conflicting results 3 …”

“…However, it was argued that the conclusions drawn by Williams et al. 18 may have been premature due to a well‐recognized publication bias in favor of reporting positive findings and often there is a considerable lag time before negative results get published 3 . The T102C polymorphism does not result in an alteration of the amino acid sequence of the protein and our data from Kuwaiti Arabs support the findings from some other populations that have shown a lack of association between this polymorphism and the onset of schizophrenia.…”

“…The syndrome manifests with multiple symptomatology involving thought, perception, emotion and global behavior and results in considerable functional impairment requiring long‐term care with frequent hospitalization 1,2 . Although twin, family and adoption studies provide overwhelming evidence of a genetic contribution to the susceptibility to schizophrenia, no susceptibility loci have been unequivocally identified to date 3 . Among several reasons for the apparent lack of success are phenotypic uncertainty, genetic heterogeneity and unclear mode of inheritance.…”

“…Among several reasons for the apparent lack of success are phenotypic uncertainty, genetic heterogeneity and unclear mode of inheritance. It has been suggested that genes of major effect are only responsible for a relatively small contribution to overall genetic risk and that major contribution comes from genes of modest effect 3 …”

“…Several lines of evidence suggest a possible role of 5‐hydroxytryptamine (5‐HT) in the etiology of schizophrenia: 3 (i) 5‐HT receptor densities and 5‐HT metabolism are found to be altered in the brains of schizophrenics; (ii) lysergide (LSD), a drug having a similar structure to that of 5‐HT, can produce a psychosis similar to schizophrenia; (iii) atypical antipsychotics, such as clozapine, have high affinity for 5‐HT receptors; and (iv) Inayama et al. 4 have reported a genetic association between schizophrenia and a serotonin receptor DNA marker (5HTR2).…”