양극성 장애 환자의 소아기 주의력결핍과 CHRNA7 유전자 다형성

Childhood Attention Deficit in the Patients with Bipolar Disorder and CHRNA7 Gene Polymorphisms

양극성 장애 환자에서 관찰되는 주의력저하에 대한 유전학적 탐구의 일환으로 본 연구에서는 양극성 장애 환자의 소아기 특성으로 나타나는 주의력결핍과 여러 측면에서 양극성 장애의 주의력과 관련이 깊을 것으로 보이는 후보유전자인 CHRNA7 유전자와의 관련성을 살펴보았다. 122명의 DSM-IV 양극성 장애 환자(양극성 장애 1형 89명, 양극성 장애 2형 33명)를 대상으로 소아기 ADHD 특성을 조사하는 WURS를 적용하고 요인분석을 시행하여 주의력결핍, 충동성, 기분불안정 의 3 가지 요인을 추출하였고 각각을 표현형으로 하여 CHRNA7 유전자 내 3개의 SNP 부위와의 관련성을 분석하였다. UNPHASED를 이용한 개별 SNP 분석 및 SNP 들의 조합을 분석한 결과 소아기 주의력결핍과는 아무런 관련성을 찾을 수 없었고 소아기 충동성 특성에 대해서는 rs2337506와 rs6494223이 개별적으로 유의하게 관련됨을 발견할 수 있었다. 향후 CHRNA7 유전자의 양극성 장애 환자의 주의력 및 소아기 특성에 미치는 역할을 규명하기 위한 후속 연구들이 필요할 것으로 사료된다.

Objective Patients with bipolar disorder have attention deficit during even euthymic status. Bipolar disorder patients showed more childhood attention deficit and other ADHD like feature. Alpha 7 nicotinic receptor (CHRNA7) gene has been known to play roles in attention and sensory gating, and association between CHRNA7 gene and bipolar disorder has been reported. Therefore, we investigated a possible association between childhood attention deficit of bipolar disorder and CHRNA7 gene polymorphisms. Methods We included 122 patients with bipolar disorder (89 subjects of bipolar disorder type I, 33 subjects of bipolar disorder type II). Childhood attention deficit was measured by Wender Utah Rating Scale (WURS). Factor analysis was done for WURS to extract inattention factor from childhood ADHD like feature. Three factors were extracted: Impulsivity, Inattention, and Mood instability. All subjects were ethnically Korean. Genotyping was done for three intronic Single Nucleotide Polymorphism (SNPs) of CHRNA7 gene: rs2337506 (A/G), rs6494223 (C/T), and rs12916879 (A/G). Analysis of association was done by UNPHASED version 3.1.4, a free software for genetic statistics. Results Genetic association tests found no association between factor score of inattention and any SNP or combination of SNPs of CHRNA7. Positive association between WURS total score and SNP rs6494223 (p=0.043), factor score of impulsivity and SNP rs2337506 (p=0.038) as well as SNP rs6494223 (p=0.043) was revealed. These positive associations were survived after 1,000 permutation tests. Combination of SNPs association tests performed for total WURS and factor scores could not find any significant association. Conclusion We could not find association between CHRNA7 gene and childhood attention deficit in bipolar disorder. However, we found CHRNA7 gene involved in childhood impulsivity of bipolar disorder, another ADHD like feature. Further studies with larger sample and denser polymorphisms are necessary to clarify genetic role of CHRNA7 in attention and impulsivity of bipolar disorder.