Xanthine oxidase activity is influenced by environmental factors in Ethiopians

被引:25
作者
Aklillu, E
Carrillo, JA
Makonnen, E
Bertilsson, L
Ingelman-Sundberg, M
机构
[1] Karolinska Inst, IMM, Div Mol Toxicol, SE-17177 Stockholm, Sweden
[2] Univ Extremadura, Sch Med, Dept Pharmacol & Psychiat, Badajoz, Spain
[3] Univ Addis Ababa, Fac Med, Dept Pharmacol, Addis Ababa, Ethiopia
[4] Karolinska Inst, Huddinge Univ Hosp, Dept Lab Med, Div Clin Pharmacol, SE-1406 Stockholm, Sweden
关键词
Ethiopians; xanthine oxidase; caffeine;
D O I
10.1007/s00228-003-0653-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objectives. To investigate xanthine oxidase (XO) polymorphism in Ethiopians and influence of environmental factors, smoking habit and gender-related differences on enzyme activity among Ethiopians living in Ethiopia or Sweden. Methods. One hundred healthy unrelated Ethiopians living in Ethiopia and 73 living in Sweden participated in the study. Subjects received a 100-mg oral dose of caffeine before bedtime. All urine voided in the following 8 h was collected and the concentrations of 1-methyluracil (1U) and 1-methylxanthine (1X) (mumol/l) were analyzed by means of high-performance liquid chromatography. The 1U/(1X+1U) metabolic ratio (MR) was calculated and used as an index of XO activity. Results. XO activity was not normally distributed (P<0.0001; Shapiro-Wilk's test). The incidence of putative XO poor metabolizers in Ethiopians was 4%. The effect of differences in country of residence, gender and smoking habit was analyzed using three-way ANOVA/MANOVA. The post-hoc test (P<0.05) and Kruskal-Wallis ANOVA (P<0.004), median test showed a significant difference in XO activity among Ethiopians living in Ethiopia compared with those living in Sweden, the activity being higher in Ethiopians living in Ethiopia. The 95% CI for differences between the two means was (0.012; 0.044). No significant difference was observed in XO MR between men and women or between smokers and non-smokers, the 95% CI for the differences being (-0.059; 0.037) and (-0.010; 0.016) respectively. Conclusion. The XO activity is polymorphic in Ethiopians. Neither gender nor smoking-related differences influenced XO activity but the difference in activity between Ethiopians living in Sweden or in Ethiopia indicates influence of other environmental factors such as dietary habits on XO activity.
引用
收藏
页码:533 / 536
页数:4
相关论文
共 25 条
  • [1] Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in Sweden
    Aklillu, E
    Herrlin, K
    Gustafsson, LL
    Bertilsson, L
    Ingelman-Sundberg, M
    [J]. PHARMACOGENETICS, 2002, 12 (05): : 375 - 383
  • [2] AKLILLU E, 2003, IN PRESS MOL PHARM
  • [3] Albuquerque RG, 2002, J TRAUMA, V53, P415, DOI 10.1097/00005373-200209000-00003
  • [4] Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy
    Cappola, TP
    Kass, DA
    Nelson, GS
    Berger, RD
    Rosas, GO
    Kobeissi, ZA
    Marbán, E
    Hare, JM
    [J]. CIRCULATION, 2001, 104 (20) : 2407 - 2411
  • [5] CAFFEINE METABOLISM IN A HEALTHY SPANISH POPULATION - N-ACETYLATOR PHENOTYPE AND OXIDATION PATHWAYS
    CARRILLO, JA
    BENITEZ, J
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1994, 55 (03) : 293 - 304
  • [6] Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine
    Carrillo, JA
    Christensen, M
    Ramos, SI
    Alm, C
    Dahl, ML
    Benítez, J
    Bertilsson, L
    [J]. THERAPEUTIC DRUG MONITORING, 2000, 22 (04) : 409 - 417
  • [7] Regulation of hepatic xanthine oxidoreductase expression by treatment of rats with xenobiotic agents.
    Cassidy, DA
    McLeod, R
    Clarke, DJ
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 1997, 25 (04) : S563 - S563
  • [8] DODION P, 1987, CANCER RES, V47, P1036
  • [9] Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure - Results from 2 placebo-controlled studies
    Doehner, W
    Schoene, N
    Rauchhaus, M
    Leyva-Leon, F
    Pavitt, DV
    Reaveley, DA
    Schuler, G
    Coats, AJS
    Anker, SD
    Hambrecht, R
    [J]. CIRCULATION, 2002, 105 (22) : 2619 - 2624
  • [10] REGULATION OF XANTHINE DEHYDROGENASE AND XANTHINE-OXIDASE ACTIVITY AND GENE-EXPRESSION IN CULTURED RAT PULMONARY ENDOTHELIAL-CELLS
    DUPONT, GP
    HUECKSTEADT, TP
    MARSHALL, BC
    RYAN, US
    MICHAEL, JR
    HOIDAL, JR
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (01) : 197 - 202