Identification of four novel polymorphisms in the calcitonin/α-CGRP (CALCA) gene and an investigation of their possible associations with Parkinson disease, schizophrenia, and manic depression

We identified novel polymorphisms in the calcitonin/CGRPα (CALCA) gene by direct sequencing of genomic DNA and subsequent genotyping by RFLP (restriction fragment length polymorphism) detection and investigated association with neurological or psychiatric disease. Four novel polymorphic alleles were found: two (g.979G>A and g.4218T>C) represented single nucleotide polymorphisms (SNPs), one consisted of two coupled SNPs in close vicinity to each other (g.1210T>C and g.1214C>G), and one was an intronic 16‐bp microdeletion (2919‐2934del16). One of the SNPs (g.4218T>C) causes a non‐synonymous amino acid change (Leu66Pro) in the third exon, an exon common to both procalcitonin and pro‐α‐CGRP. In a subsequent association study, frequencies of the identified polymorphisms in Parkinson and schizophrenia patients were compared with frequencies in the normal population. No statistically significant association was found in our material. The 16‐bp microdeletion polymorphism was present in a family with multiple cases of unipolar or bipolar depressive disorder. Using this polymorphism as marker, cosegregation with the phenotype was observed in the majority of individuals. Hum Mutat 17:435‐436, 2001. © 2001 Wiley‐Liss, Inc.