The Association between Trans, Trans-Muconic Acid as a Biomarker for Benzene Exposure and the Platelet Count

벤젠노출 지표로써 요중 뮤콘산과 혈소판 수치의 연관성

  • Min, Young-Sun (Department of Occupational Medicine, Soonchunhyang University Kumi Hospital) ;
  • Woo, Kuck-Hyun (Department of Occupational Medicine, Soonchunhyang University Kumi Hospital) ;
  • Kim, Jin-Seok (Department of Occupational Medicine, Soonchunhyang University Kumi Hospital) ;
  • Yoo, Jay-Young (Department of Occupational Medicine, Soonchunhyang University Kumi Hospital) ;
  • Lee, Kwan (Department of Preventive Medicine, Dongguk University College of Medicine) ;
  • Lim, Hyun-Sul (Department of Preventive Medicine, Dongguk University College of Medicine) ;
  • Kim, Heon (Department of Preventive Medicine, Chungbuk National University College of Medicine)
  • 민영선 (순천향대학교 구미병원 산업의학과) ;
  • 우극현 (순천향대학교 구미병원 산업의학과) ;
  • 김진석 (순천향대학교 구미병원 산업의학과) ;
  • 유재영 (순천향대학교 구미병원 산업의학과) ;
  • 이관 (동국의대 예방의학교실) ;
  • 임현술 (동국의대 예방의학교실) ;
  • 김헌 (충북의대 예방의학교실)
  • Received : 2010.02.17
  • Accepted : 2010.04.08
  • Published : 2010.06.30

Abstract

Objective: Recent researches suggest that trans,trans-muconic acid (t,t-MA) would be an adequate metabolic biomarker for low-level benzene exposure. Few study have investigated the association between the t,t-MA and platelet count, and this is the primary aim of this study. Methods: From May 2004 to June 2004, 326 chemical factory workers took part in a questionnaire survey and they underwent urinary t,t-MA and CBC assessment. The questionnaire covered general aspects of health and the occupational and smoking histories. Statistical analyses of outcomes were performed using SPSS 14.0 for Windows. Results: The subjects' urinary t,t-MA concentration (geometric mean and geometric standard deviation) was 0.28 mg/g creatinine (2.62). No significant differences between different occupations among the chemical workers were found. The urinary t,t-MA concentrations in the smokers and non-smokers were 0.32 mg/g creatinine (2.44) and 0.25 mg/g creatinine (2.77) respectively, and the difference was statistically significant (p<0.05). There was no significant difference in the platelet count based on occupation and the smoking history. There was significant correlation between log(platelet) and log(t,t-MA)(r=-0.116 p=0.039). The regression equation log(platelet) = -0.002${\times}$Age + [-0.029${\times}$log(t,t-MA)] + 2.436, R2=0.032, was calculated from linear regression analysis with log(platelet) as the dependent variable. Cross-tabulation between 2 subgroups that were divided by the 90-percentile level of the t,t-MA (0.819 mg/g creatinine), and 2 subgroups that were divided by the 10-percentile level of the platelet count (175,000) was conducted. Higher distribution in subgroup with platelet count below 175,000 was demonstrated in the subgroup with a urinary t,t-MA above the 90-percentile, with an odds ratio of 3.01. Conclusions: The study may be limited by not taking into account factors such as smoking quantity and sorbic acid, which may confound urinary the t,t-MA concentration as well as medication and infection that may affect the platelet count. Yet it is meaningful that the correlation between the urinary t,t-MA concentration and the platelet count was found through linear regression analysis and the chi-square test, and further, this outcome may be used as a basis for a study to establish the acceptable limit of urinary t,t-MA in Korea.

목적: 최근 저농도 벤젠노출의 적절한 지표로써 요중 trans,trans-muconic acid(t,t-MA)가 여러 연구에서 제안되고 있으나, 혈소판 수치와의 관련성 연구는 거의 없는 실정이다. 이에 이들의 연관성을 파악하고자 이 연구를 시행하였다. 방법: 2004년 5월부터 6월까지 카보머, 카본블랙 등을 생산하며 일부 공정에서 벤젠을 취급하는 화학공장 근로자 326명에 대한 설문조사, 요중 뮤콘산, 혈액검사 등을 시행하였다. 설문조사는 일반적 사항을 포함하여 작업력, 흡연습관 등을 조사하였으며, 요중 뮤콘산의 농도는 HPLC를 이용하여 분석하였고, 혈액은 자동혈구분석기로 분석하였다. 모든 자료는 전산 입력하였고, 통계분석은 SPSS 14.0 for Windows를 이용하였다. 결과: 조사 대상자의 요중 뮤콘산 기하평균(기하표준편차) 농도는 0.28 mg/g creatinine(2.62)이었고, 직종에 따른 차이는 없었다. 흡연자의 요중 뮤콘산의 기하평균(기하표준편차) 농도는 0.32 mg/g creatinine (2.44)으로 비흡연자의 0.25 mg/g creatinine(2.77)보다 유의하게 높다(p<0.05). 조사 대상자의 직종 및 흡연유무에 따른 혈소판수의 차이는 없었다. log(platelet)과 log(t,t-MA)은 유의한 상관관계가 있었고(r=-0.116, p=0.039), log(platelet)를 종속변수로 하는 선형회귀분석에서 log(platelet)= -0.002${\times}$Age + [-0.029${\times}$log(t,t-MA)] +2.436, R square=0.032의 회귀식을 산출하였다. 뮤콘산 90분위수(0.819 mg/g creatinine) 기준에서 두 군으로 나눈 변수와 혈소판 10분위수(175,000개)를 기준에서 두 군으로 나눈 변수를 이용해 실시한 카이제곱 검증에서, 뮤콘산 90분위수(0.819 mg/g creatinine 기준) 초과군이 이하군에 비해 혈소판 17만5천 이하 분포가 교차비 3.01로 유의하게 높았다. 결론: 이 연구는 뮤콘산과 혈소판 수치의 상관관계에 있어 흡연의 정량화, 소르빈산과 같은 요중 뮤콘산 농도에 영향을 미치는 인자, 약물이나 감염과 같은 혈소판에 영향을 미치는 인자 등을 정확히 보정하지 못한 제한점이 있지만, 요중 뮤콘산과 혈소판 수치와의 관련성을 선형회귀분석과 교차분석 등을 통하여 유의한 상관성을 관찰하였고, 향후 요중 뮤콘산 농도의 기준치 설정에 대한 참고 자료를 제시하였다는 점에서 의의가 있다.

Keywords

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