2007;28:916-922 J Korean Acad Fam Med 원저 혈중 γ-gt 와고혈압 을지대학교의과대학가정의학교실 정성섭ㆍ최희정ㆍ한경희ㆍ김상환 연구배경 : 이미우리나라남성을대상으로 γ-gt 의상승과고혈압의연관성에대해대규모연구가진행되었으나, 남녀를대상으로하여연구된것은없었다. 이에저자들은한대학병원에서실시하였던건강검진자료를분석하여혈중 γ-gt 와고혈압의관련성을알아보고자하였다. 방법 : 2004 년 4 월부터 2005 년 4 월까지건강증진센터를방문한 20 세이상성인남녀중, B 형및 C 형간염보유자와간기능에영향을줄수있는약물을복용하는사람을제외한 3,070 명을대상으로하였다. 설문지와문진을통해대상자들의과거병력과현재병력, 현재복용중인약물에대해조사하였고, 기본적인신체검사와검사실검사를시행하였다. 결과 : 혈중 γ-gt 를사분위수로나누어분류하였을때, 남녀모두에서 γ-gt 의분류단계가올라갈수록흡연, 음주, 체질량지수, 복부둘레, 수축기및이완기혈압, 공복혈당, 총콜레스테롤, 중성지방, 저밀도지질단백이증가하였다 (P for trend <0.01). γ-gt 가최고사분위수에해당하는경우최저사분위수에해당하는경우에비해고혈압의위험이남성에서는 1.6 배 (95% CI, 1.0 2.3), 여성에서는 1.6 배 (95% CI, 1.0 2.4) 증가하였다. 결론 : 이연구에서는심혈관계질환에영향을미칠수있는요인들을통제하고도남녀모두에서혈중 γ-gt 가최고사분위수에해당하는경우최저사분위수에해당하는경우에비해고혈압의위험이증가하였다. 중심단어 : 고혈압, 감마지티피, 간기능, 심혈관질환 서 γ-gt (gamma-glutamyltransferase) 는세포외막에있는효소로세포내의항산화작용에중요한역할을한다. γ- GT 는특히간에많이분포하여간세포에손상을주는인자들에의해증가하며 1-4) 알코올섭취정도를예측하는지표로도널리이용되고있다. 5) 알코올섭취나간세포손상으로인해혈중 γ-gt 가증가하는것은간세포의산화스트레스가증가하는것에기인한다고알려져있다. 간세포가산화스트레스를받으면간세포막에존재하는 γ-gt 가세포밖에존재하는글루타티온을분해하여세포내에필요한가용아미노산을얻게되는데, 간질환이나알코올섭취, 약물등에의해자유라디칼이증가되면글루타티온이고갈되고이를보상하기위해 γ-gt 합성이증가한다. 4,6) 접수일 : 2006 년 8 월 31 일, 승인일 : 2007 년 11 월 16 일 교신저자 : 김상환 Tel: 042-611-3229, Fax: 042-611-3776 E-mail: fanin@eulji.ac.kr 론 다수의연구에따르면혈중 γ-gt 는심혈관질환의위험인자와밀접한관계가있으며 7-12), 일부연구에서는 γ- GT 가심혈관질환이나뇌혈관질환의발생에독립적인위험인자로작용한다고보고하고있다. 13) 또한알코올섭취가증가할수록고혈압의발생위험이높다고알려져있기때문에 14-16) 알코올섭취에따른 γ-gt 의상승이고혈압과관련이있을것으로생각할수있으나 γ-gt 와혈압이알코올섭취와는독립적으로관계가있었다고보고한것도있다. 16,17) γ-gt 의상승과고혈압의연관성에대하여는기존에우리나라남성을대상으로한대규모연구결과가있었으나 18), 남녀를대상으로연구된것은없었다. 또한혈중 γ-gt 가기본적인검사의필수항목으로포함되어많이측정을하고있음에도불구하고, 단지간기능이상이나알코올섭취의지표로만해석하는경우가많았다. 이에저자들은한대학병원에서실시하였던건강검진자료를분석하여혈중 γ-gt 와고혈압의관련성을알아보고자하였다. 916
정성섭외 : 혈중 γ-gt 와고혈압 1. 연구대상 방 이연구는 2004 년 4 월부터 2005 년 4 월까지건강검진을위해한대학병원의건강증진센터를방문한 20 세이상의성인남녀 3,462 명중, HBs Ag 양성자와 Anti-HCV Ab 양성자를제외나간기능에영향을줄수있는약물을복용하고있는자, 그리고 AST, ALT 가 100 IU/L 이상인경우는제외하였다. 또한 WBC count >10,000/mm 3 과같은염증성질환및상태가의심되는경우를제외한 3,070 법 명을대상으로하였다. 2. 연구방법 설문지와의사의문진을통해대상자들의과거병력과현재병력, 현재복용중인약물에대해조사하였다. 흡연력은현재흡연자와비흡연자로구분하였고, 음주력은음부여부와주당음주횟수, 1 회음주량을확인하였고, 주당음주횟수와 1 회음주량을이용하여주당평균알코올섭취량을계산하였다. 음주를하지않는군과주당 72 g 미만인군, 그리고주당 72 g 이상인군으로나누었다. 운동력은주당운동횟수를조사하였다. Table 1. General characteristics of subjects. Unit: No (%), mean±s.d. Variables Male (n=1370) Female (n=1700) P value* Age (yr) Hypertension (%) Diabetes (%) Coronary heart disease (%) Current smoker (%) Alcohol None 72 g/week > 72 g/week Exercise (time/week) Coffee (cup/day) Body mass index (kg/m 2 ) Waist circumference (cm) Hip circumference (cm) Waist-to-hip ratio Body fat (%) Systolic blood pressure (mmhg) Diastolic blood pressure (mmhg) Fasting blood sugar (mg/dl) AST (IU/L) ALT (IU/L) Alkaline phosphatase (IU/L) γ-gt (IU/L) Blood urea nitrogen (mg/dl) Creatinine (mg/dl) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) C-reactive protein (mg/dl) 47.8±11.5 491 (35.8) 160 (5.2) 6 (0.4) 579 (42.3) 304 (22.2) 1055 (77.0) 11 (0.8) 1.4±2.0 1.6±1.6 24.3±3.0 86.4±7.9 96.9±5.5 0.89±0.05 21.8±4.8 132.9±16.2 78.8±10.8 96.3±23.1 27.1±8.8 29.4±14.8 71.1±19.3 51.1±49.2 15.0±3.7 1.0±0.1 199.1±35.2 165.4±123.7 49.9±11.2 110.0±29.0 0.16±0.30 45.7±13.6 454 (26.7) 98 (5.8) 5 (0.3) 73 (4.3) 1036 (60.9) 658 (38.7) 6 (0.4) 1.2±1.9 1.0±1.1 23.4±3.4 78.8±9.1 95.2±5.7 0.83±0.07 30.0±5.3 127.1±19.2 73.0±11.5 90.2±18.3 22.7±7.3 19.2±10.5 65.6±23.5 20.8±25.7 13.6±3.9 0.8±0.1 196.6±37.1 116.0±79.4 55.9±12.8 107.7±29.5 0.14±0.34 0.555 0.026 0.060 0.030 *P value by t-test (continuous variables) or χ 2 -test (categorical variables). Tested by Fisher's exact chi-square test, Values have been analysed after log-transformation. Vol. 28, No. 12 917
Sung-Sub Jung, et al: Serum γ-gt and Hypertension 기본적인신체검사와검사실검사를위한채혈은측정전최소 12 시간이상금식을하도록한후, 다음날오전 8 시에서 9 시 30 분사이에시행하였다. 신체계측으로는신장과체중을측정하였고, WHO 권고사항에따라허리둘레를측정하였다. 19) 또한생체전기저항법을이용한체성분분석기 (Inbody 4.0, Biospace, Korea) 를이용하여체지방량과체지방률, 제지방량, 내장지방면적등을측정하였다. 체질량지수는 Quetelet Index 를이용하여체중 (kg) 을신장 (m 2 ) 으로나누어계산하였다. 혈압은대상자가최소 10 분이상안정을하도록한후, 앉은자세에서자동혈압측정기 (BP-8800C, Colin electronics Co. LTD, Japan) 를이용하여두번측정하였고, 측정한혈압의평균값을취하였다. 채혈한혈액은 3 시간내검사실로보내분석하였고, 공복혈당, AST (aspartate aminotransferase), ALT (alanine aminotransferase), γ-gt, 혈액요소질소, 크레아티닌, 총콜레스테롤, 중성지방, 고밀도지질단백, 저밀도지질단백, C 반응단백등을측정하였다. 고혈압은수축기혈압이 140 mmhg 이상이거나이완기혈압이 90 mmhg 이상인경우또는현재고혈압약물을복용중인경우로정의하였고, JNC 7 분류기준 20) 에따라정상혈압과전단계고혈압, 고혈압의 3 군으로분류하였 으며, 혈중 γ-gt 는남성과여성각각의사분위수를이용하여 4 군으로나누어분석하였다. 3. 통계분석 남녀대상자의일반적인특성과이들특성의차이는범주형변수인경우카이제곱검정을, 연속형변수인경우 T- 검정을통해분석하였다. γ-gt 에따른건강행태와혈압, 심혈관질환과관련된혈액및생화학지표의차이를알아보기위해 P for trend 검정을하였다. 또한다중로지스틱회귀분석을이용하여 γ-gt 가고혈압에영향을주는지를알아보았다. 분석에사용한통계프로그램은 SAS for windows (version 9.0) 이었고, 통계적유의수준은 0.05 이하로하였다. 결 과 1. 연구대상자의일반적인특성 연구대상자 3,070 명중남성은 1,370 명 (45%), 여성은 1,700 명 (55%) 이었다. 대상자의평균연령은남성이 47.8 ±11.5 세, 여성이 45.7±13.6 세이었다. γ-gt 의중간값은남성에서 35.0 (24.0 60.0) IU/L, 여성에서 16.0 (12.0 Table 2. Mean of selected covariates by level of γ-gt in men. Units: No (%), mean±s.d. Covariates γ-gt (IU/L) <24 (n=340) 24 35 (n=328) 35 60 (n=353) 60 (n=349) P for trend Age (yr) 48.7±13.0 47.6±12.3 47.5±10.5 47.6±10.1 0.176 Current smoker (%) 119 (35.0) 121 (36.9) 152 (43.1) 187 (53.6) Alcohol drinking (%) 214 (62.9) 238 (72.6) 286 (81.0) 328 (94.0) Exercise (times/week) 1.4±2.1 1.5±2.0 1.4±1.9 1.2±1.9 0.603 Coffee (cup/day) 1.6±1.7 1.6±1.6 1.7±1.6 1.6±1.5 0.512 Body mass index (kg/m 2 ) 22.5±2.4 24.2±2.8 25.0±2.7 25.7±2.9 Waist circumference (cm) 81.4±7.0 85.7±7.6 88.1±7.1 90.2±6.9 Systolic BP (mmhg) 127.7±15.7 130.7±14.7 135.6±15.6 137.5±17.0 Diastolic BP (mmhg) 74.8±10.3 77.0±9.4 81.2±10.5 82.0±11.2 Fasting sugar (mg/dl) 91.3±16.1 93.5±19.0 98.2±25.7 101.8±27.8 Total cholesterol (mg/dl) 187.8±31.4 196.4±36.3 203.8±33.1 208.0±36.3 Triglyceride (mg/dl)* 113.4±125.4 140.9±89.5 174.9±99.1 229.6±141.4 HDL-cholesterol (mg/dl) 51.0±11.1 49.2±10.6 49.5±12.3 50.1±10.6 0.081 LDL-cholesterol (mg/dl) 105.8±25.9 110.8±30.0 114.1±29.3 109.3±30.1 C-reactive protein (mg/dl)* 0.14±0.31 0.15±0.29 0.14±0.19 0.21±0.38 *Values have been analysed after log-transformation. 918
정성섭외 : 혈중 γ-gt 와고혈압 21.5) IU/L 로남성에서여성에비해유의하게높았다 (P <0.01). 이외에도연령, 고혈압, 당뇨병, 음주량, 흡연량, 커피섭취량, 체질량지수, 허리둘레, 체지방률, AST, ALT, 수축기및이완기혈압, 크레아티닌, 총콜레스테롤, 고밀도지질단백, 공복혈당, C 반응단백등이여성에비해남성에서유의하게높은것으로나타났다 (P<0.05) ( 표 1). 2. 남녀에서 γ-gt 사분위수에따른생활습관및심혈관관련지표의차이 남녀를각각 γ-gt 의사분위수에따라네군으로분류하였을때, 남성에서연령, 주당운동횟수, 고밀도지질단백은 γ-gt 분류단계에따라유의한차이가없는것으로나타났다. 그러나음주량, 흡연량, 체질량지수, 수축기및이완기혈압, 공복혈당, 총콜레스테롤, 중성지방, 저밀도지질단백은 γ-gt 의분류단계가올라갈수록유의하게증가하였고, 각군간에유의한차이가있었다 (P for trend <0.01) ( 표 2). 한편, 여성에서는 γ-gt 의분류단계가올라갈수록고밀도지질단백을제외한모든변수가 유의하게증가한반면 (P for trend<0.01), 고밀도지질단백은유의하게감소하였다 (P for trend 0.02) ( 표 3). 3. 혈압분류에따른감마지티피의차이 대상자의현재병력과혈압을이용하여 JNC 7 분류기준에따라정상혈압과전단계고혈압, 고혈압의 3 군으로분류하고각군에서 log (γ-gt) 의평균치를비교하였을때, 혈압의분류단계가올라감에따라 log (γ-gt) 가증가하였으며, 각군간에는유의한차이가있었다 (P<0.01) ( 그림 1). 4. 고혈압에대한 γ-gt 의영향 고혈압이 γ-gt 에미치는영향을분석하기위해종속변수를고혈압으로하고 γ-gt 를네군으로나누어다중로지스틱회귀분석을시행하였다. 나이, 체질량지수, 흡연, 음주, 공복혈당, 중성지방, 저밀도지질단백, C 반응단백을통제하였을때 γ-gt 가최고사분위수에해당하는경우최저사분위수에해당하는경우에비해고혈압의 Table 3. Mean of selected covariates by level of γ-gt in women. Units: No (%), mean±s.d. γ-gt (IU/L) Covariates <13 (n=433) 13 17 (n=484) 17 23 (n=400) 23 (n=383) P for trend Age (years) 40.2±14.0 44.4±13.7 48.8±12.7 50.2±11.1 Current smoker (%) 14 (3.2) 13 (2.7) 18 (4.5) 28 (7.3) Alcohol drinking (%) 183 (42.3) 205 (42.4) 148 (37.0) 128 (33.4) Exercise (times/week) 1.1±1.8 1.2±1.9 1.5±2.1 1.1±1.9 0.015 Coffee(cup/day) 1.0±1.1 0.9±1.2 1.0±1.1 1.0±1.2 0.864 Body mass index (kg/m 2 ) 22.1±2.8 24.2±2.8 23.8±3.3 25.2±3.6 Waist circumference (cm) 74.9±7.8 85.7±7.6 80.1±8.7 83.7±9.2 Systolic BP (mmhg) 121.2±16.9 125.3±18.7 129.3±18.5 133.9±20.7 Diastolic BP (mmhg) 69.0±10.5 72.2±11.7 74.4±10.4 77.0±11.7 Fasting sugar (mg/dl) 86.0±8.9 87.6±11.1 90.7±15.6 97.8±30.0 Total cholesterol (mg/dl) 183.9±34.0 193.1±33.5 201.2±35.2 210.8±40.8 Triglyceride (mg/dl)* 84.4±46.8 105.9±70.1 122.9±75.8 157.3±101.7 HDL-cholesterol (mg/dl) 57.0±12.5 57.2±13.1 54.9±13.0 54.0±12.5 0.022 LDL-cholesterol (mg/dl) 99.5±26.3 104.4±27.5 112.0±28.8 116.8±33.0 C-reactive protein (mg/dl)* 0.09±0.26 0.10±0.17 0.16±0.40 0.21±0.49 *Values have been analysed after log-transformation. Vol. 28, No. 12 919
Sung-Sub Jung, et al: Serum γ-gt and Hypertension 위험이남성에서 1.6 배 (95% CI, 1.0 2.3), 여성에서 1.6 배 (95% CI, 1.0 2.4) 증가하는것으로나타났다 ( 표 4). 고 이연구에서는남녀모두에서혈중 γ-gt 가최저사분위수에속하는군보다최고사분위수에속하는경우고 Figure 1. Level of γ-gt according to grade of hypertension. 찰 혈압의위험이증가하는것으로나타났다. 기존의연구에서심혈관계질환의여러위험인자에해당하는체질량지수, 운동, 중성지방, 총콜레스테롤, 공복혈당이 γ- GT 와관련이있었다는보고가있었으며 11,12), 몇몇연구에서는혈중 γ-gt 가커피섭취량과관련이있다고보고하였지만 21,22), 이연구에서는남녀모두커피섭취량과혈중 γ-gt 간에관련이없는것으로나타났다. Nilssen 등 8) 은여성에서혈중 γ-gt 가혈압과약한양의상관관계를나타내었으나, 남성에서는이러한관련성이없다고하였고, Yamada 등 23) 은음주자에서만혈중 γ-gt 가고혈압의유병률과관련이있을뿐, 비음주자에서는관련이없었다고하였다. 그러나 Stranges 등 17) 이혈중 γ-gt 가정상인사람들을대상으로한연구에서알코올섭취에관계없이혈중 γ-gt 가고혈압의발생과상관관계가있었고, 그상관관계는음주자보다비음주자에서더강한것으로보고하였다. 또한과체중이나복부비만을가지는사람에서혈중 γ-gt 는고혈압발생의예측인자라고하였다. 이연구에서는알코올섭취나비만과는독립적으로남녀모두에서혈중 γ-gt 가높을수록고혈압의위험이증가하는것으로나타났는데, 이는대상자의연령이나성별, 인종, 분석방법의차이에기인한것으로생각한다. Table 4. Odd ratios (95% confidence interval) for hypertension by γ-gt groups. γ-gt groups Quartile 1 Quartile 2 Quartile 3 Quartile 4 P for trend All subject n 772 771 756 771 Model 1* 1 1.3 (1.0 1.7) 1.4 (1.1 1.8) 2.4 (1.8 3.1) Model 2 1 1.9 (1.5 2.5) 2.6 (2.1 3.4) 5.0 (3.9 6.4) Model 3 1 1.2 (0.9 1.7) 1.2 (0.9 1.6) 1.7 (1.3 2.4) 0.002 Male n 340 328 353 349 Model 1* 1 0.9 (0.6 1.4) 1.4 (0.9 1.9) 2.0 (1.4 2.9) Model 2 1 1.2 (0.9 1.7) 1.9 (1.4 2.7) 3.1 (2.2 4.4) Model 3 1 0.9 (0.6 1.3) 1.2 (0.8 1.7) 1.6 (1.0 2.3) 0.011 Female n 433 484 400 383 Model 1* 1 1.4 (0.9 2.1) 1.5 (1.0 2.3) 2.2 (1.5 3.3) Model 2 1 1.9 (1.3 2.7) 3.0 (2.1 4.2) 5.0 (3.5 7.1) Model 3 1 1.3 (0.8 1.9) 1.3 (0.9 2.0) 1.6 (1.0 2.4) 0.056 *Adjusted for age and body mass index, Adjusted for alcohol, Adjusted for age, body mass index, alcohol, smoking, fasting sugar, triglyceride, Ldl-cholesterol, C-reactive protein. 920
정성섭외 : 혈중 γ-gt 와고혈압 남성만을대상으로했던국내의한연구에서는 γ-gt 가 30 IU/L 이상인경우 30 IU/L 미만인경우에비해고혈압의유병률이높았으며, 이러한현상은음주자에서만나타났다고하였다. 18) 그러나이연구에서는남녀모두에서 γ-gt가최고사분위수에속하는경우 ( 남성 60 IU/L, 여성 23 IU/L) 최저사분위수에속하는경우 ( 남성 <24 IU/L, 여성<13 IU/L) 에비해음주를통제하였을때고혈압의발생위험이남녀에서각각 3배, 5배증가하는것으로나타나, 이러한결과가음주와는무관한것으로보인다. 혈중 γ-gt가증가하는것은간세포에부하되는산화스트레스가중요한기전으로작용한다. 간세포막에존재하는 γ-gt는세포가산화스트레스를받을때세포외부에존재하는글루타티온을분해하여세포내에필요한가용아미노산을얻는데관여하기때문에간질환이나알코올섭취, 약물등에의해유리자유기가증가되면글루타티온이고갈되면서이를보상하기위해 γ-gt의합성이증가하는것으로알려져있다. 4,6) 산화스트레스는심혈관계질환, 당뇨병, 비만, 운동부족, 흡연, 지질대사이상등에서도혈중 γ-gt의상승과관련성이있는것으로알려져있을뿐아니라 4,11,12,23), γ-gt는염증인자인섬유소원이나 C반응단백과관련이있다는보고도있다. 24) 이러한기전으로혈중 γ-gt가고혈압발생에영향을주는것을설명할수도있겠으나, 아직까지혈중 γ- GT과고혈압의관계를명확하게설명할수있는기전은밝혀져있지않다. 이연구의제한점은대상자가일반적인우리나라남녀를대표하지못한다는것이다. 즉, 건강검진을위해건강증진센터에방문한사람들을대상으로하였기때문에누구보다스스로의건강상태에대해관심이높은사람일가능성이높아, 이연구결과를일반인에확대적용하는데주의가필요하다. 또한이연구는단면연구이기때문에혈중 γ-gt와고혈압의인과관계를추론할수없다는제한도있다. 이연구에서는고혈압에영향을미칠수있는여러요인들을통제하고도혈중 γ-gt가남성에서 60 IU/L 이상, 여성에서 23 IU/L 이상인경우고혈압의위험이증가함을보여주었다. 따라서혈중 γ-gt가증가한현상을간기능이상이나알코올섭취와관련하여해석하는데국한하지말고고혈압의위험도증가할수있다는점을고려해야할것이다. 또한향후에는혈중 γ-gt과고혈압의관련성을설명할수있는기전에대한연구도이루어져야할필요가있다. ABSTRACTS Serum γ-gt and Hypertension Sung-Sub Jung, M.D., Hee-Jeong Choi, M.D., Ph.D., Kyung- Hee Han, M.D., Sang-Hwan Kim, M.D., M.P.H. Department of Family Medicine, Eulji University School of Medicine, Daejeon, Korea Background: We analyzed the data obtained from regular health checkups performed in a university hospital and investigated the effect of serum γ-gt on hypertension for both Korean males and females. Methods: A total of 3,288 adult males and females over 20 years of age were selected for this study who visited a health promotion center from April, 2004 to April, 2005. Patients with HBs Ag (+) or anti-hcv Ab (+) and those currently on medication that could affect hepatic function were excluded. The subjects' history of illness and their present health and medication status were examined through questionnaires and history taking. Also, basic physical examinations and laboratory tests were performed on these subjects. Results: Classifying the serum γ-gt into quartiles, as the γ-gt classification stage increased, there was an increase in the amount of smoking, alcohol, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride and low density lipoprotein for males or female (respectively, P for trend <0.01). When odd ratio (95% CI) for hypertension in the highest quartile of γ-gt was compared to that of the lowest quartile, there was an increased risk of hypertension with an odd ratio of 1.6 (95% CI, 1.0 2.3) and 1.6 (95% CI, 1.0 2.4) for males and females, respectively. Conclusion: This study showed that the risk of hypertension was increased according to serum γ-gt, even though the variable index affecting cardiovascular diseases was adjusted. (J Korean Acad Fam Med 2007; 28:916-922) Key words: hypertension, γ-gt, hepatic function, cardiovascular disease Vol. 28, No. 12 921
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