Possible association of a cholecystokinin promoter variant to schizophrenia

Am J Med Genet. 2002 Jul 8;114(5):479-82. doi: 10.1002/ajmg.10408.


Several lines of research indicate a cholecystokinin (CCK) deficit in schizophrenia patients. A C to T substitution was found in the promoter region of the CCK gene. We investigated this promoter variant in patients with schizophrenia and geographically-matchedcontrols. The T allele was detected in 24% of the 85 schizophrenics and 16% of the 247 controls. No significant difference in the T allele frequency was found between patients and controls (chi(2) = 2.77, P > 0.1). The schizophrenia sample was analyzed further along the dimensions of positive and negative symptoms. The patients with prominent negative symptoms presented a statistically significant association to the T allele (chi(2) = 4.13, P < 0.04). However, the significance disappeared after the Bonferroni correction (P > 0.15). Since the case-control analysis may present incorrect ethnic match between cases and controls, we applied the family-based tests to verify the above findings. Both transmission disequilibrium test (TDT; chi(2) = 5.33, P < 0.025 in 12 trios) and haplotype relative risk (HRR; chi(2) = 3.844, P < 0.05 in 60 trios) indicated a significantly high transmission of T allele to schizophrenia offspring probands from their parents. While our family-based tests seem to support the CCK involvement in schizophrenia, no definite conclusion can be drawn based on such a small sample size. This preliminary finding is subjected to future investigations.

MeSH terms

  • Alleles
  • Cholecystokinin / genetics*
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Gene Frequency
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Phenotype
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic / genetics*
  • Schizophrenia / genetics*


  • DNA
  • Cholecystokinin