Lack of an association between SNPs within the cholinergic receptor genes and smoking behavior in a Czech post-MONICA study

Smoking has a significant heritable component of approximately 30–60%. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) within the nicotinic cholinergic receptor subunits 3 (rs578776), 5 (rs16969968) and β3 (rs6474412), which are associated with nicotine dependence in Western European populations. To analyze the association in a Czech population, we genotyped 1,191 males and 1,368 females (post-MONICA study). The WHO protocol was used to examine smoking status and the number of cigarettes smoked per day. There were 32.1% current and 27.6% past smokers among the males and 22.5% current and 13.8% past smokers among the females. We have not confirmed the original results: the SNPs rs16969968 (p = 0.07), rs578776 (p = 0.16) and rs6474412 (p = 0.76) were not associated with smoking status (never-smokers vs. ever-smokers) in the entire population, if a codominant model of analysis was used. This result was valid for both the male and female subpopulations if analyzed separately and adjusted for age. Finally, in ever-smokers, the number of cigarettes smoked per day was also independent of different genotypes, regardless of which polymorphism (and gender) was analyzed (the lowest p value was 0.49). The association between the cholinergic receptors–nicotinic subunits (-3, -5 and -ß3), and smoking behavior may be population-dependent.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

     

Tau gene mutation in familial progressive subcortical gliosis

Familial forms of frontotemporal dementias are associated with mutations in the tau gene. A kindred affected by progressive subcortical gliosis (PSG), a rare form of presenile dementia, has genetic linkage to chromosome 17q21-22. This kindred (PSG-1) is included in the 'frontotemporal dementias and Parkinsonism linked to chromosome 17' group along with kindreds affected by apparently different forms of atypical dementias. Some of these kindreds have mutations in the tau gene. We report here that PSG-1 has a tau mutation at position +16 of the intron after exon 10. The mutation destabilizes a predicted stem-loop structure and leads to an over-representation of the soluble four-repeat tau isoforms, which assemble into wide, twisted, ribbon-like filaments and ultimately result in abundant neuronal and glial tau pathology. The mutations associated with PSG and other atypical dementias can be subdivided into three groups according to their tau gene locations and effects on tau. The existence of tau mutations with distinct pathogenetic mechanisms may explain the phenotypic heterogeneity of atypical dementias that previously led to their classification into separate disease entities.