PubMed · 11809218
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H L McLeod. 2002-01-05. Pharmacokinetic differences between ethnic groups.. https://doi.org/10.1016/s0140-6736(02)07296-3
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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) micromol/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.
BACKGROUND: SP-A, SP-B, and SP-D are pulmonary surfactant proteins. Several linkage and association studies have been done using these genes as markers to locate pulmonary disease susceptibility genes, but few have studied the markers systematically in different ethnic groups. Here we studied eight markers in SP-A, SP-B, and SP-D genes in seven ethnic groups from three races (Caucasian, Black and Hispanic). We measured the similarity of the marker distribution among the ethnic groups in order to see whether people in different ethnic groups or races could be mixed together for linkage and association studies. To evaluate the usefulness of these markers, we estimated the informativeness of each marker loci in the seven ethnic groups by assessing their heterozygosity and PIC values. We also conducted linkage disequilibrium (LD) analysis to identify associated marker loci and to estimate the haplotype frequencies in each of the seven ethnic groups in an attempt to find valuable haplotypes so that the level of polymorphism of the "markers" could be increased. RESULTS: Our findings indicate that allele and genotype frequencies may be different between different ethnic groups, especially between ethnic groups from different races. The markers are in general polymorphic in a variety of study groups, especially for the two SP-A1 and SP-A2 markers. Two-locus LD analysis reveals that three pairs of loci are strongly associated together: B-18(A/C) with B1013(A/C), DA11(C/T) with DA160(A/G), SP-A1 with SP-A2. Three-locus LD analysis suggests that B-18(A/C), B1013(A/C) and B1580(C/T) are strongly associated with each other. CONCLUSIONS: Allele and genotype frequency differences imply that different ethnic groups should be mixed with extreme caution before performing linkage and association studies. The associated markers could be used together to increase the level of polymorphism and the informativeness of the "markers".
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