국내 흡연자에서 유전자 다형성과 금연결과와의 관계
The Association between DNA Polymorphisms and Smoking Cessation in Korean Smokers
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연구배경: 흡연 관련 행동과 유전적 변이가 연관이 있다는 것이 최근 많은 연구에서 제시되고 있다. 저자들은 국내 흡연자들을 대상으로 금연 결과에 영향을 미칠 수 있다고 알려진 니코틴 관련 유전자들의 다형성에 대해 조사하였다. 방법: 2009년 3월부터 8월까지 한 대학병원 외래에 내원한 금연을 원하는 흡연자 51명을 대상으로 내원시 흡연특징, 사회 경제적 요인, 음주 상태 등을 문진으로 확인하고,1년간 추적 관찰하여 금연 여부를 확인하였다. 또한, 대상자의 구강 점막 검체를 채취하여 니코틴 대사와 연관된 유전자인 dopamine D2 receptor (DRD2) TaqI, DRD2 -141C,dopamine D4 receptor (DRD4), serotonin transporter (5-HTT)의 다형성을 조사하고, 금연 성공군과 실패군 사이에 빈도를 조사하였다. 금연 성공은 6개월 째 금연 상태에 있는 경우로 정의하였다. 결과: 금연 성공에 도달한 대상자는 18명(35.3%)이었다. 금연 성공군이 실패군에 비해 음주를 하고 있는 경우가 많았고, 호흡기 증상인 기침은 금연 실패군에서 유의하게 더높은 빈도로 나타났다. 금연과 연관된 유전자의 다형성 중도파민 경로와 관련된 DRD2 TaqI (Al allele)와 DRD2-141C (Ins C allele)의 빈도는 두 군 사이에 차이를 보이지않았다. 또한, DRD4의 variable number of tandem repeat (VNTR), 5-HTT의 유전자 다형성의 빈도도 두 군간 비슷한 분포를 나타내었다. 결론: 본 연구는 비록 많지 않은 대상자를 조사하였다는한계점을 지니고 있으나, 니코틴 관련 유전자들인 DRD2TaqI, DRD2 -141C, DRD4 VNTR, 5-HTT의 다형성이 금연 성공군과 실패군 사이에 큰 차이가 없음을 보여주었다.
Abstract
Background: Recent research demonstrates a strong association between smoking-related behaviors and genetic variation. We investigated the clinical features and genetic effects of dopamine receptors and a serotonin transporter on smoking cessation in Koreans. Methods: Smokers (n=51) wanting to quit smoking were included as the study population. They were genotyped for polymorphisms in dopamine D2 receptor (DRD2) (TaqI and -141C), dopamine D4 receptor (DRD4),and a serotonin transporter (5-HTT). We defined abstinence as stopping smoking at six months after enrollment. Results: Eighteen patients (35.3%) stopped smoking at six months. The abstinence group had a higher rate of alcohol use whereas the non-abstinence group had more coughing. However, there were no significant differences in average smoking rate, starting age of smoking, gender, nicotine dependence, and forced expiratory volume in one second between the two groups. As for the genes in the dopamine pathway, the polymorphisms of DRD2 TaqI (A1 allele) and DRD2 -141C (Ins C allele) were not genotypically different between the two groups (P=0.245 and 0.409, respectively). The genetic variation in the DRD4 variable number of tandem repeats (VNTR) also showed a similar distribution in the two groups. Regarding the polymorphisms of 5-HTT,there was no difference in the long allele between the two groups (P=0.852). Conclusions: This study suggests that the genetic variations of DRD2 TaqI, DRD2 -141C, DRD4 VNTR, and 5-HTT might have little influence on smoking cessation in Korean smokers.
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