Association Analysis of CYP2A6 Gene Variant (rs1801272A>T) with Nicotine Metabolism and Smoking Tendency Among Pakistani Youth

BackgroundCytochrome P450 2A6 (CYP2A6) is a key enzyme in nicotine metabolism, with its genetic variants playing a role in smoking behavior. Particularly, g.40848628A>T is significantly associated with nicotine metabolism and smoking tendency in different populations. The purpose of the current study is to examine the genetic diversity of this locus and association analysis within smokers and non-smokers cohorts among Pakistani youth. Methods and ResultsThe allele-specific ARMS PCR genotyping technique was applied to examine a total of 100 samples as a case-control study of n=50 from each cohort. From the sampled individuals, 92% were found to be homozygous wild-type (AA), 7% were heterozygous (AT), and 1% were homozygous mutant (TT). PLINK software was used for the Chi-square test yielded, {chi}2 (1, N = 100) = 2.91, p = .088 suggesting a non-significant trend towards association, where alternative allele frequencies were calculated as 0.07 and 0.02 in cases & control cohorts respectively. Similarly, Hardy-Weinberg Equilibrium (HWE) p = 0.1714 indicates genotype frequencies did not significantly deviate from HW expectations and no error or selection in the overall samples. The carriers of the alternative allele have 3.688 times higher odds of being affected by the condition compared to non-carriers with the reference allele. ConclusionsFuture studies with larger sample size may help to clarify the population structure of the subject locus. Genome-wide association studies using next-generation sequencing may also aid in predicting nicotine metabolism and resistance to smoking cessation in the Pakistani population.