We found that the major allele homozygotes (CC) of – 26C/T polymorphism of AMPK γ2 gene might be protective against cognitive impairment during aging while minor allele homozygotes (TT) more vulnerable to diabetes. With some inevitable limitations of a cross-sectional population study, our data
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collectively support a hypothesis that AMPK gene polymorphism is a common contributing factor involved in both cognitive and metabolic dysfunctions in humans, and also suggest in part that cognitive impairment in diabetes might not be totally dependent on the vascular dysfunction secondary to diabetes. An extended and longitudinal study with multiple target SNPs is warranted.
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ABSTRACT(IN KOREAN)
인지기능 및 당뇨병과 관련된 AMPK 감마2 유전자 PRKAG2의 유전다형성
<지도교수 오 병 훈>
연세대학교 대학원 의학과
김 어 수
대사장애 및 인지장애는 서로 깊이 연관되어 있는 것으로 밝혀지고 있으나, 그 연관성에 대한 구체적인 기전에 대해서는 논란 중이다.
AMP-활성 단백질 인산화효소(AMP-activated protein kinase, AMPK)는
에너지대사의 중추적 조절 효소다. 에너지대사의 이상은
알츠하이머병을 포함한 인지감퇴와 대사질환, 양쪽 모두에 중요한 병인론으로 주목받고 있다. 따라서 본 연구에서는 AMPK 감마2 유전자의 단일유전다형성(PRKAG2 -26 C/T polymorphism)이 대한민국 지역사회 노인(60세 – 80세)의 인지기능 및 당뇨병과 관련되는지를 조사하였다. 나이, 성별, 교육연수, 흡연력, 음주력, 우울점수, 허리둘레, APOE e4 유전자형의 개수 등을 통제한 다변량 로지스틱 회귀분석에서 -26 C/T 유전다형성은 인지장애와 유의한 관계가 있음이 밝혀졌다(CC 대 CT/TT, OR, 1.6; 95% CI, 1.1-2.2). 더 나아가, 이는
29
당뇨병의 존재와도 연관된 것으로 밝혀졌다 (CC/CT 대 TT, OR, 1.8;
95% CI, 1.2-2.8). 중요한 것은, 당뇨가 없는 노인들을 대상으로 분석을 반복했을 때도 이 유전다형성과 인지기능과의 관계가 유의하게 관찰되었다는 것이다. 추가적인 소그룹 분석에서 CC 유전형을 가진 사람들은 CT/TT군 보다 언어 및 시각 즉각/지연 회상과 주의력 검사에서 유의하게 높은 평균점수를 보였다. 본 연구결과는 AMPK가
당뇨에 의한 이차적인 인지감퇴를 배제하더라도, 인지장애와
대사장애에 동시에 영향을 미치는 공통인자라는 것을 시사한다. 향후 더 큰 집단에서 전향적 연구를 통해 이러한 결과를 확인해야 할 것이다.