Genetic Polymorphisms In The Cyp2a6: Implications For Inter-Individual Differences In Nicotine Metabolism
| dc.contributor.author | MUSA, NURFADHLINA | |
| dc.date.accessioned | 2016-08-16T07:05:48Z | |
| dc.date.available | 2016-08-16T07:05:48Z | |
| dc.date.issued | 2006 | |
| dc.description.abstract | CYP2A6 is polymorphic. It metabolizes nicotine, cotinine, several pro-carcinogens and drugs. Variant CYP2A6 alleles reduced risks for smoking and Caucasian have lower frequencies for the PM phenotype than Asians. The objective of our study was to develop analytical and molecular genetic methods for studying CYP2A6 polymorphism in Malaysia. Subjects were healthy adult Malays, Chinese and Indians who gave informed consents. DNA was extiacted from blood using salting out procedures and subjected to PCR-genotyping for CYP2A6. Six-hundred and sixteen subjects were enrolled. The frequencies for CYP2A6*1 A, CYP2A6*1 B, CYP2A6*4, C YP2A 6*5, CYP2A6*7, C YP2A 6*8, CYP2A6*10 and CYP2A6*1x2 among Malays were 27.04%, 46.67%, 7.04%, 0.93%, 4.26%, 5.00%, 4.26% and 0.37% respectively; among Chinese, 34.30%, 44.48%, 4.94%, 1.16%, 6.98%, 1.45%, 1.74% and 1.45% respectively and among Indians were 52.01%,39.37%, 0.29%, 1.15%, 1.44%, 0.86% and 0.86% respectively. CYP2A6*3 was also detected among Indians. We also used an HPLC to determine nicotine and cotinine from plasma of 40 volunteers administered nicotine. A probit plot of log MR for nicotine was obtained. Sub populations exist suggesting existence of a polymorphism at the CYP2A6 locus. We conclude that we successfully developed methods for the population study of CYP2A6 polymorphism in Malaysia. Our allelespecific PCR was not only specific and sensitive but was also less tedious compared to published methods. Applied to the three major ethnic groups in Malaysia we noted heterogeneity in the polymorphism and the presence of CYP2A6*3 among Indians. Our HPLC methods were sufficiently specific and sensitive as proven by validating against seeded controls and using in a p!/ot project with 40 subjects in whom CYP2A6 polymorphism was evident. The ethnic differences we showed in our Malaysian population may imply different ethnic susceptibility to certain diseases and adverse effects of drugs. Further studies are however required using larger sample sizes. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/2413 | |
| dc.subject | Genetic Pol Ymorphisms In The Cyp2a6: Implications For | en_US |
| dc.subject | Inter-Individual Differences In Nicotine Metabolism | en_US |
| dc.title | Genetic Polymorphisms In The Cyp2a6: Implications For Inter-Individual Differences In Nicotine Metabolism | en_US |
| dc.type | Thesis | en_US |
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