Cholecystokinin A Receptor Gene Promoter Polymorphism and Intelligence

Purpose

To study the association between Cholecystokinin A receptor (CCKAR) genotypes and intelligence in community-living men and women.

Method

Subjects were 2251 community-dwelling Japanese men and women aged 40 to 79 years. The CCKAR gene promoter polymorphisms A-81G and G-128T were determined. Intelligence was assessed by Japanese Wechsler Adult Intelligence Scales – Revised Short Forms (JWAIS-R SF). The difference in intelligence between wild type and mutation was tested.

Results

There were no subjects with AA/GT, AA/TT, or AG/TT genotypic combinations. Both A-81G and G-128T genotypes were related to intelligence quotient (IQ) estimated by JWAIS-R SF. The mean and SE of IQ levels of subjects with the wild-type allele and the mutation allele at nucleotide -128 were 103.4 ± 0.3 and 101.6 ± 0.6, respectively. There was a significant difference in IQ for G-128T (p=0.008). The difference in IQ for A-81G was also significant (p=0.011). The IQ level was 103.6 ± 0.4 in the subjects with the wild-type allele and 102.0 ± 0.5 in the subjects with the mutation. Differences in IQ levels by haplotypes for combinations of A-81G/G-128T were examined. IQ significantly decreased with an increasing number of mutation alleles (p=0.018).

Conclusion

There were statistically significant differences in IQ for CCKAR gene promoter polymorphisms A-81G and G-128T in community-living Japanese.

Key words: Cholecystokinin, Intelligence, Genotype, Epidemiology

Selected Abbreviations and Acronyms: BMI, body mass index, CCK, cholecystokinin, CCKAR, cholecystokinin A receptor, CNS, central nervous system, DNA, deoxyribonucleic acid, GLM, general linear model, IQ, intelligence quotient, JWAIS-R-SF, Japanese Wechsler Adult Intelligence Scales – Revised Short Forms, NILS-LSA, National Institute for Longevity Sciences – Longitudinal Study of Aging, PCR-RFLP, polymerase chain reaction – restriction fragment length polymorphism, OLETF, Otsuka Long-Evans Tokushima Fatty, SE, standard error, WAIS-R, Wechsler Adult Intelligence Scales – Revised