Cigarette Smoking Behavior a Gateway to Opium Use Disorder: A Mendelian Randomization Analysis.

Gateway hypothesis presumes that using a psychotropic drug can increase the probability of using another drug. The study was to assess whether cigarette smoking is a gateway drug for subsequent opium use. Mendelian randomization (MR) analysis was applied to test and estimate the size of causal effect of cigarette smoking on opium use. The CHRNA3 rs1051730 polymorphism was used as an instrumental variable. A population-based case control study in the setting of Fasa Cohort Study was carried out using 477 cases and 531 controls based on their opium use status at the baseline of cohort study. The logistic two stage estimator method was applied. The Number of cigarettes smoked per day was associated with opium use (OR 1.17, 95% CI 1.15-1.19). In the MR analysis, rs1051730 T alleles were associated with increased risk of opium use among ever smokers (OR 5.73, 95% CI 1.72-19.07) however there found no evidence of association among never smokers. In instrumental variable analysis, showed that on average smoking every 1 more cigarette per day increases the odds of opium use by 1.17 (OR 1.17, 95%CI:1.14-1.19). The MR analysis found a positive finding on the relationship between cigarette smoking and opium use which supports the gateway hypothesis. It adds new information to the gateway theory regarding the relation of cigarette smoking and drug use, and increases our understanding of the importance of tobacco control for prevention of opium addiction.

Molecular Genetic Analysis of Steroid Resistant Nephrotic Syndrome, Detection of a Novel Mutation.

INTRODUCTION: Nephrotic syndrome is a heterogeneous disease in children, with nearly 10% categorized as steroid-resistant. In this study we evaluated disease related mutations within NPHS1, NPHS2 and new potential variants in other genes. METHODS: In the first phase of study, 25 patients with SRNS were analyzed by Sanger sequencing for NPHS1 (exon 2, 26) and all exons of NPHS2 genes. In the next step, whole exome sequencing was performed on 10 patients with no mutation in NPHS1 and NPHS2. RESULTS: WES analysis revealed a novel mutation in FAT1 (c.10570C > A; Q3524K). We identified 4 pathogenic mutations, located in exon 4 and 5 of NPHS2 gene in 20% of patients (V180M, P118L, R168C and Leu156Phe). Also our study has contributed to the description of previously known pathogenic mutations across WT1 (R205C) and SMARCAL1 (R764Q) and a novel polymorphism in CRB2. CONCLUSION: It seems that NPHS2, especially exons 4 and 5, should be considered as the first step in genetic evaluation of Iranian patients. We suggest conducting WES after NPHS2 screening to identify the potential genes associated with SRNS, Further studies are required to examine more common genes in the first step and then designing native laboratory panels.

The association between polymorphism of the BDNF gene and cigarette smoking in the Iranian population.

BACKGROUND: Cigarette smoking remains a serious public health problem. Environmental and genetic factors both play critical roles in the process of cigarette smoking. We aimed to investigate the associations between single nucleotide polymorphisms (SNP) in the BDNF gene and cigarette smoking in the Iranian population. METHODS: We conducted a case-control study. In total, 932 case and control subjects aged > 15 years were recruited in the present study in a simple random manner, including 523 lifetime cigarette smokers, 466 cigarette smokers within a 12-month period, 409 never cigarette smokers in their lifetime and 466 never cigarette smokers within a 12-month period. The rs6265 SNP genotypes were determined by a polymerase chain reaction followed by restriction fragment length polymorphism. To examine the association of smoking with the BDNF gene polymorphism, odds ratios (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and sex. RESULTS: In total, 932 participants (758 males and 174 females) were selected. Using a chi-squared test, we found that rs6265 with OR = 1.41 and 95% CI = 1.07-1.87 (p = 0.009) and OR = 1.41 and 95% CI = 1.08-1.85 (p = 0.008) in the BNDF was associated with an increased odds of lifetime cigarette smoking and cigarette smoking within a 12-month period, respectively. Also, the allele "A" of rs6265 in BDNF had a significant elevating effect for cigarette smoking in a recessive model (p < 0.05). CONCLUSIONS: These results suggest that polymorphisms of BDNF play an important role in lifetime cigarette smoking and cigarette smoking within a 12-month period of susceptibility in the Iranian population.