Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia

Hong Seock Lee, Seung Hyun Kim, Heon Jeong Lee, Leen Kim, Sang Kyu Lee, Dong Won Jang, Min Soo Lee, Bong Gi Son, Kwang Yoon Suh, Sangduk Kim

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23 Citations (Scopus)


We examined the genetic effect of DRD2 A1 allele in 167 Korean schizophrenics in relation to their smoking habit. Although there was no apparent difference in the genotype distributions of DRD2 gene among the female schizophrenics (n = 66), the male counterpart (n = 101) showed significant differences in their genotype distributions. The comparison between male smoking and nonsmoking patients showed the difference in genotype distribution (P = 0.010) with a higher prevalence of A1 allele (P = 0.020) and frequency of heterozygotes (P = 0.005), but not frequency of the A1 allele. The A1A2 heterozygotes male showed significantly higher smoking rate compared to the A1A1 or A2A2 homozygotes male, and non-smokers were deficient in heterozygotes. By contrast, among female schizophrenics, the heterozygotes showed a lower smoking rate than homozygotes and there were more heterozygotes in non-smokers. The deviation from Hardy-Weinberg expectations was observed in male and female non-smokers showing quite opposite profiles. Highly significant differences were seen between male and female non-smokers in A1 prevalence (P = 0.001), genotype distribution (P = 0.00011), and frequency of heterozygotes (P = 0.00003), but not in A1 frequency. The analyses from both male and female as one group showing no significant difference in the genotype distributions between smokers and non-smokers could be explained by the gender difference in the genetic effect of DRD2 A1 allele. Our findings present the gender-specific molecular heterosis of DRD2 gene in relation specifically to the smoking status of schizophrenic patients. They indicate the importance of heterosis and gender effects that should be taken into consideration for the association studies.

Original languageEnglish
Pages (from-to)593-597
Number of pages5
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Issue number6
Publication statusPublished - 2002 Aug 8


  • DRD2 gene
  • Gender-specific
  • Heterozygote advantage
  • Nicotine dependence
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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