to the 55M allele. The -108C allele has greater promoter activity than the -108T allele which results in different serum activities. The distribution of the PON1 polymorphisms varies with ethnicity. The frequency of the PON1-192R allele increases the further from Europe a population originates, the frequency in Caucasians of 15-30% increases to 70-90% in Far Eastern Oriental and Sub-Saharan African populations. In the southern US African-Americans are five times more likely to be RR than Caucasians. In contrast the PON1-55M allele is much less frequent in Oriental and black African populations compared to Caucasians and are extremely rare or absent in some populations e.g. Thais. These ethnic differences in SNP distribution can lead to large activity differences between populations. Clinical significance PON1 was first discovered through its ability to hydrolyse and therefore detoxify organophosphorus compounds which are widely used as pesticides and nerve gases. Despite decades of research it is only now becoming clear that PON1 protects humans from the acute and chronic harmful effects of these compounds. Low PON1 activity found in children may increase their susceptibility to organophosphates. However, the greatest research interest has been the role of PON1 in atherosclerosis, where, because of its ability to remove harmful oxidised-lipids, PON1 protects against the development of atherosclerosis Oxidized polyunsaturated fatty acids (notably in oxidized low-density lipoprotein) form lactone-like structures that are PON substrates. PON1 also protects against bacterial infection by destroying the bacterial signalling molecules that cause gram negative bacteria to invade human tissue and form colonies, thus PON1 contributes to the bodies innate immunity. Recently it has been suggested that PON1 has a role in healthy aging, however, the mechanism is currently unknown. PON1 activity is low in infants compared to adults. A study of Mexican-American children showed that PON1 activity increased 3.5 times between birth and age seven. An association between PON1 gene polymorphism and susceptibility to Parkinson's disease was not found in a Chinese population. Notes References Further reading