Lee Hong-Seock, Kim Seung-Hyun, Lee Heon-Jeong, Kim Leen, Lee Sang-Kyu, Jang Dong-Won, Lee Min Soo, Son Bong-Gi, Suh Kwang-Yoon, Kim Sangduk
Department of Psychiatry, College of Medicine, Korea University Hospital, Seoul, Korea.
Am J Med Genet. 2002 Aug 8;114(6):593-7. doi: 10.1002/ajmg.10641.
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.
我们研究了167名韩国精神分裂症患者中DRD2 A1等位基因的遗传效应与其吸烟习惯的关系。虽然女性精神分裂症患者（n = 66）中DRD2基因的基因型分布没有明显差异，但男性患者（n = 101）的基因型分布存在显著差异。男性吸烟患者与不吸烟患者的基因型分布比较显示出差异（P = 0.010），A1等位基因的患病率较高（P = 0.020），杂合子频率较高（P = 0.005），但A1等位基因频率无差异。A1A2杂合子男性的吸烟率显著高于A1A1或A2A2纯合子男性，且不吸烟者中杂合子较少。相比之下，在女性精神分裂症患者中，杂合子的吸烟率低于纯合子，且不吸烟者中杂合子更多。在男性和女性不吸烟者中观察到偏离哈迪-温伯格预期的情况，表现出完全相反的模式。男性和女性不吸烟者在A1患病率（P = 0.001）、基因型分布（P = 0.00011）和杂合子频率（P = 0.00003）方面存在高度显著差异，但A1频率无差异。将男性和女性作为一组进行分析，吸烟者和不吸烟者的基因型分布没有显著差异，这可以用DRD2 A1等位基因遗传效应的性别差异来解释。我们的研究结果表明DRD2基因在精神分裂症患者吸烟状态方面存在性别特异性分子杂种优势。它们表明杂种优势和性别效应的重要性，在关联研究中应予以考虑。
