한국인 알코올의존환자에서의 제1형 부신피질자극 호르몬 분비 촉진 호르몬수용체의 유전자 다형성에 관한 연구
Association Study of Corticotropine-Releasing Hormone Recepter 1(CRHR1)Gene Polymorphism in Korean Alcohol-Dependent Patients
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참고문헌
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초록
스트레스 반응에 중요한 역할을 하고 있는 CRHR1 유전자 SNP와 알코올 의존과의 연관성에 관한 선행 연구들이 있다. 이에 본 연구는 백인을 대상으로 조사했던 기존연구와는 달리 한국인 남녀를 대상으로 하여 알코올 의존군과 정상 대조군의 CRHR1 유전자형 빈도 및 대립유전자형 빈도를 비교하였다. 본 연구의 연구대상자들은 알코올 의존군 268명(남자 218명, 여자 50명)과 정상대조군 137명(남자 78명, 여자 59명)이었다. CRHR1 유전자 SNP를 SNP database와 선행연구를 근거로 선정한 후, 연구 대상자들의 이러한 SNP 유전자형을 PCR-RFLP방법으로 조사하였다. 그 결과, 한국인의 CRHR1 유전자 SNPs로 7개(rs242938, rs404623, rs28364027, rs16940686, rs937, rs878886, rs878887)가 분석되었다. 이중 rs28364027의 A 대립 유전자의 빈도는 남녀 각각에서 알코올 의존군이 대조군보다 유의하게 높았다. 그리고 rs28364027의 AA 유전자형 및 A 대립 유전자와 rs878886의 CC유전자형 및 C 대립유전자의 빈도는 알코올 의존군내에서 여성이 남성보다 유의하게 높았다. 이러한 결과를 종합해 보면 CRHR1 유전자 SNP가 알코올 의존의 유전적 원인의 중요한 요인일 가능성을 제시하고 있다. 또 이러한 CRHR1 유전자 SNP가 알코올 의존의 유전적 원인에서 남녀간 차이를 설명할 수 있을 가능성도 시사하고 있다.
Abstract
Objectives：There were several preceding studies investigating the association between alcohol dependence and corticotropine releasing hormone receptor1(CRHR1) gene SNPs that play an important role in response to stress. The frequencies of CRHR1 genotypes and alleles were compared between alcohol-dependent patients and normal control subjects. Methods：The subjects were 268 alcohol-dependent patients(218 males, 50 females) and 137 normal controls(78 male, 59 female). CRHR1 gene SNPs were investigated according to the SNP database and the results from previous studies, and their genotypes were analyzed by polymerase chain reaction(PCR) and restriction fragment length poly-morphism(RFLP). Results：Seven CRHR1 gene SNPs(rs242938, rs404623, rs28364027, rs16940686, rs937, rs878886, rs878887) were found in Korean subjects. The frequency of rs28364027 A allele was significantly higher in alcohol-dependent patients than normal controls in both genders. In alcohol-dependent patients, the frequencies of AA genotype and A allele of rs28364027, and of CC genotype and C allele of rs878886 were higher in female than male. Conclusion：These results suggest that CRHR1 gene SNP is one of the important genetic factors in the etiology of alcohol dependence. And also it is supposed that the different frequency of SNP genotype could explain stress-related gender difference in the genetic etiology of alcohol dependence.
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