Endocrine Abstracts

Cigarette smoking is the major cause of disease related deaths in the world. Cigarette smoke contains many harmful chemicals, among them nicotine is the most potent one. The root cause of smoking hazards is nicotine addiction or dependence (ND). Environmental as well as genetic factors are reported to influence smoking which leads to nicotine addiction in all age groups especially. Neurexin1 is a cell adhesion protein important for synapse formation and CHRNB4 is cholinergic receptor beta polypeptide. Studies have revealed a strong association between nicotine addiction and genetic variants in NRXN 1 and CHRNB4 genes in different world populations. Genetic associations of rs6721498 and rs17487223 SNPs of NRXN1 and CHRNB4 genes with ND were explored in Pakistani tobacco smokers. The questionnaire based data and blood and were collected from three hundred (300) individuals belonging to different ethnicities of Pakistan and categorized into non-smokers and smokers and habitual smokers. Based on Fagerstrom test, smokers and habitual smokers were categorized as Nicotine dependent and non-dependent. DNA was extracted and PCR-RFLP based genotyping of rs6721498 and rs17487223 SNPs performed for. Allele and genotyping frequencies were calculated and their associations with nicotine dependence was estimated. Association of nicotine dependence with anthropometric variables was also calculated. Allele Frequency of minor allele (A) of rs6721498 was 0.74 in nicotine dependent subjects and homozygous A/A genotype minor allele (A) increased risk of ND by 10.5 folds while allele frequency of minor allele (T) of rs17487223 was 0.56 and homozygous T/T genotype of minor allele (T) increased risk of ND by 8.44 folds. The socio-economic factors like education and tea/coffee intake increased risk of developing N.D by 5.76 and 3.32 times respectively while age, income status, ethnicity, Family history, stimulus, and obesity lacked significance of associations. Based on the highly strong associations of the minor alleles of both SNPs with nicotine addiction, it could be concluded that rs6721498 of NRXN1 and rs17487223 of CHRNB4 gene SNPs are risk markers of exploring nicotine dependence in Pakistani smokers. The environmental/socioeconomic parameters like caffeine intake and education also expressed significant association with ND. Subjects with Punjabi and Pothohari were more at risk of ND as compared to Pathan and other ethnic groups of Pakistan. Present study signifies role of genetic as well as environmental/socioeconomic risk factors that could lead to ND.