Variant within the promoter region of the CHRNA3 gene associated with FTN dependence is not related to self-reported willingness to quit smoking.

INTRODUCTION: Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region is robustly associated with smoking quantity. Conversely, the association between one of the most significant single nucleotide polymorphisms (SNPs; rs1051730 within the CHRNA3 gene) with perceived difficulty or willingness to quit smoking among current smokers is unknown. METHODS: Cross-sectional study including current smokers, 502 women, and 552 men. Heaviness of smoking index (HSI), difficulty, attempting, and intention to quit smoking were assessed by questionnaire. RESULTS: The rs1051730 SNP was associated with increased HSI (age, gender, and education-adjusted mean ± SE: 2.6 ± 0.1, 2.2 ± 0.1, and 2.0 ± 0.1 for AA, AG, and GG genotypes, respectively, p < .01). Multivariate logistic regression adjusting for gender, age, education, leisure-time physical activity, and personal history of cardiovascular or lung disease showed rs1051730 to be associated with higher smoking dependence (odds ratio [OR] and 95% CI for each additional A-allele: 1.38 [1.11-1.72] for smoking more than 20 cigarette equivalents/day; 1.31 [1.00-1.71] for an HSI ≥5 and 1.32 [1.05-1.65] for smoking 5 min after waking up) and borderline associated with difficulty to quit (OR = 1.29 [0.98-1.70]), but this relationship was no longer significant after adjusting for nicotine dependence. Also, no relationship was found with willingness (OR = 1.03 [0.85-1.26]), attempt (OR = 1.00 [0.83-1.20]), or preparation (OR = 0.95 [0.38-2.38]) to quit. Similar findings were obtained for other SNPs, but their effect on nicotine dependence was no longer significant after adjusting for rs1051730. Conclusions: These data confirm the effect of rs1051730 on nicotine dependence but failed to find any relationship with difficulty, willingness, and motivation to quit.

Chromosomal gene movements reflect the recent origin and biology of therian sex chromosomes

Mammalian sex chromosomes stem from ancestral autosomes and have substantially differentiated. It was shown that X-linked genes have generated duplicate intronless gene copies (retrogenes) on autosomes due to this differentiation. However, the precise driving forces for this out-of-X gene "movement" and its evolutionary onset are not known. Based on expression analyses of male germ-cell populations, we here substantiate and extend the hypothesis that autosomal retrogenes functionally compensate for the silencing of their X-linked housekeeping parental genes during, but also after, male meiotic sex chromosome inactivation (MSCI). Thus, sexually antagonistic forces have not played a major role for the selective fixation of X-derived gene copies in mammals. Our dating analyses reveal that although retrogenes were produced ever since the common mammalian ancestor, selectively driven retrogene export from the X only started later, on the placental mammal (eutherian) and marsupial (metatherian) lineages, respectively. Together, these observations suggest that chromosome-wide MSCI emerged close to the eutherian-marsupial split approximately 180 million years ago. Given that MSCI probably reflects the spread of the recombination barrier between the X and Y, crucial for their differentiation, our data imply that these chromosomes became more widely differentiated only late in the therian ancestor, well after the divergence of the monotreme lineage. Thus, our study also provides strong independent support for the recent notion that our sex chromosomes emerged, not in the common ancestor of all mammals, but rather in the therian ancestor, and therefore are much younger than previously thought

Evolution of vitellogenin genes: comparative analysis of the nucleotide sequences downstream of the transcription initiation site of four Xenopus laevis and one chicken gene.

Electron microscopic analysis of heteroduplexes between the most distantly related Xenopus vitellogenin genes (A genes X B genes) has revealed the distribution of homologous regions that have been preferentially conserved after the duplication events that gave rise to the multigene family in Xenopus laevis. DNA sequence analysis was limited to the region downstream of the transcription initiation site of the Xenopus genes A1, B1 and B2 and a comparison with the Xenopus A2 and the major chicken vitellogenin gene is presented. Within the coding regions of the first three exons, nucleotide substitutions resulting in amino acid changes accumulate at a rate similar to that observed in globin genes. This suggests that the duplication event which led to the formation of the A and B ancestral genes in Xenopus laevis occurred about 150 million years ago. Homologous exons of the A1-A2 and B1-B2 gene pairs, which formed about 30 million years ago, show a quite similar sequence divergence. In contrast, A1-A2 homologous introns seem to have evolved much faster than their B1-B2 counterparts.

SNCA, MAPT, and GSK3B in Parkinson disease: a gene-gene interaction study.

Background and purpose:  Recent evidence suggests that variation in the SNCA, MAPT, and GSK3B genes interacts in affecting risk for Parkinson disease (PD). In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD. Methods:  Three Caucasian PD patient-control series from the United States, Ireland, and Norway (combined n = 1020 patients and 1095 controls) were genotyped for SNCA rs356219, MAPT H1/H2-discriminating SNP rs1052553, and GSK3B rs334558 and rs6438552. Results:  Our findings indicate that as previously reported, the SNCA rs356219-G allele and MAPT rs1052553 (H1 haplotype) were both associated with an increased risk of PD, whilst contrary to previous reports, GSK3B variants were not. No pair-wise interaction was observed between SNCA, MAPT, and GSK3B; the risk effects of SNCA rs356219-G and MAPT rs1052553-H1 were seen in a similar manner across genotypes of other variants, with no evidence suggesting synergistic, antagonistic, or deferential effects. Conclusions:  In the Caucasian patient-control series examined, risk for PD was influenced by variation in SNCA and MAPT but not GSK3B. Additionally, those three genes did not interact in determining disease risk.