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OBJECTIVE To investigate the effect of the functional CD14 promoter polymorphism on serum liver function tests and abnormally elevated liver function tests in a general population sample. METHODS We recruited 310 subjects at random from general practitioner lists in Surrey. A previously validated medical questionnaire was completed and a serum sample provided for estimation of liver function test and genotyping of CD14 promoter polymorphism. RESULTS The TT polymorphism was associated with significantly reduced serum levels of alanine aminotransferase 0.49 (95% confidence interval 0.26-0.93), gamma-glutamyl transferase 0.49 (95% confidence interval 0.38-0.89) and aspartate aminotransferase 0.48 (95% confidence interval 10.38-0.89). The TT polymorphism was associated with a reduced frequency of liver function test abnormalities, especially gamma-glutamyl transferase (odds ratio 0.113; 0.015-0.851). CONCLUSION The TT promoter polymorphism was associated with reduced serum levels of alanine aminotransferase, gamma-glutamyl transferase and aspartate aminotransferase in healthy patients, and a low level of liver function test abnormalities. The relationship with gamma-glutamyl transferase stands after correction for age, gender, obesity and alcohol consumption. This raises the possibility that this genotype may offer protection from the development of fatty liver disease.