Influences of polymorphic variants of DRD2 and SLC6A3 genes, and their combinations on smoking in Polish population

<p>Abstract</p> <p>Background</p> <p>Polymorphisms in dopaminergic genes may influence cigarette smoking by their potential impact on dopamine reward pathway function. <it>A1 </it>allele of <it>DRD2 </it>gene is associated with a reduced dopamine D2 receptor density, and it has been hypothesised that <it>A1 </it>carriers are more vulnerable to smoking. In turn, the 9-repeat allele of dopamine transporter gene (<it>SLC6A3</it>) has been associated with a substantial reduction in dopamine transporter, what might result in the higher level of dopamine in the synaptic cleft, and thereby protective role of this allele from smoking. In the present study we investigated whether polymorphic variants of <it>DRD2 </it>and <it>SLC6A3 </it>genes and their combinations are associated with the smoking habit in the Polish population.</p> <p>Methods</p> <p>Genotyping for <it>Taq</it>I<it>A </it>polymorphism of <it>DRD2 </it>and <it>SLC6A3 </it>VNTR polymorphism was performed in 150 ever-smokers and 158 never-smokers. The association between the smoking status and smoking phenotypes (related to the number of cigarettes smoked daily and age of starting regular smoking), and genotype/genotype combinations was expressed by ORs together with 95% CI. Alpha level of 0.05, with Bonferroni correction whenever appropriate, was used for statistical significance.</p> <p>Results</p> <p>At the used alpha levels no association between <it>DRD2 </it>and <it>SLC6A</it>3 genotypes and smoking status was found. However, <it>A1 </it>allele carriers reported longer abstinence periods on quitting attempts than non-carriers (p = 0.049). The ORs for heavier smoking were 0.38 (0.17-0.88), p = 0.023, and 0.39 (0.17-0.88), p = 0.021 in carriers compared to non-carriers of <it>A1 </it>or <it>*9 </it>allele, respectively, and the OR for this smoking phenotype was 8.68 (2.47-30.46), p = 0.0005 for the <it>A1</it>-/<it>9</it>- genotype combination, relatively to the <it>A1</it>+/<it>9</it>+. Carriers of <it>*9 </it>allele of <it>SLC6A3 </it>had over twice a lower risk to start smoking before the age of 20 years compared to non-carriers (sex-adjusted OR = 0.44; 95% CI: 0.22-0.89; p = 0.0017), and subjects with <it>A1-/9- </it>genotype combination had a higher risk for staring regular smoking before the age of 20 years in comparison to subjects with <it>A1+/9+ </it>genotype combination (sex-adjusted OR = 3.79; 95% CI:1.03-13.90; p = 0.003).</p> <p>Conclusion</p> <p>Polymorphic variants of <it>DRD2 </it>and <it>SLC6A3 </it>genes may influence some aspects of the smoking behavior, including age of starting regular smoking, the level of cigarette consumption, and periods of abstinence. Further large sample studies are needed to verify this hypothesis.</p

The Dopamine Transporter Gene, a Spectrum of Most Common Risky Behaviors, and the Legal Status of the Behaviors

This study tests the specific hypothesis that the 9R/9R genotype in the VNTR of the dopamine transporter gene (DAT1) exerts a general protective effect against a spectrum of risky behaviors in comparison to the 10R/9R and 10R/10R genotypes, drawing on three-time repeated measures of risky behaviors in adolescence and young adulthood on about 822 non-Hispanic white males from the Add Health study. Our data have established two empirical findings. The first is a protective main effect in the DAT1 gene against risky behaviors. The second finding is that the protective effect varies over age, with the effect prominent at ages when a behavior is illegal and the effect largely vanished at ages when the behavior becomes legal or more socially tolerated. Both the protective main effect and the gene-lifecourse interaction effect are replicated across a spectrum of most common risky behaviors: delinquency, variety of sexual partners, binge drinking, drinking quantity, smoking quantity, smoking frequency, marijuana use, cocaine use, other illegal drug use, and seatbelt non-wearing. We also compared individuals with the protective genotype and individuals without it in terms of age, physical maturity, verbal IQ, GPA, received popularity, sent popularity, church attendance, two biological parents, and parental education. These comparisons indicate that the protective effect of DAT1*9R/9R cannot be explained away by these background characteristics. Our work demonstrates how legal/social contexts can enhance or reduce a genetic effect on risky behaviors

Quantity and quality of childcare and children’s educational outcomes

Policy-makers wanting to support child development can choose to adjust the quantity or quality of publicly funded universal pre-school. To assess the impact of such changes, we estimate the effects of an increase in free pre-school education in England of about 3.5 months at age 3 on children’s school achievement at age 5. We exploit date-of-birth discontinuities that create variation in the length and starting age of free pre-school using administrative school records linked to nursery characteristics. Estimated effects are small overall, but the impact of the additional term is substantially larger in settings with the highest inspection quality rating but not in settings with highly qualified staff. Estimated effects fade out by age 7

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1), additional CFEOM1 families, and a reduction of the critical region on chromosome 12.

Poster presentation at the 2000 Meeting of AAPOS in San Diego, C

Identification Of Kif21A Mutations As A Rare Cause Of Congenital Fibrosis Of The Extraocular Muscles Type 3 (Cfeom3)

PURPOSE. Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype.WoSScopu

IDENTIFICATION OF KIF21A MUTATIONS AS A RARE CAUSE OF CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES TYPE 3 (CFEOM3).

PURPOSE: Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS: All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS: Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS: The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype