Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia.
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 non-smoking 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.
Lee
Hong-Seock
HS
Department of Psychiatry, College of Medicine, Korea University Hospital, Seoul, Korea. lhs242@hanmail.net
Kim
Seung-Hyun
SH
Lee
Heon-Jeong
HJ
Kim
Leen
L
Lee
Sang-Kyu
SK
Jang
Dong-Won
DW
Lee
Min Soo
MS
Son
Bong-Gi
BG
Suh
Kwang-Yoon
KY
Kim
Sangduk
S
D000483:Alleles; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006823:Hybrid Vigor; D008297:Male; D016133:Polymerase Chain Reaction; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000235:genetics*
D017931:DNA Primers; D017448:Receptors, Dopamine D2