Relationship of common variants in CHRNA5 with early-onset schizophrenia and executive function.

Altered cholinergic neural transmission is hypothesized to increase susceptibility to cognitive deficits in psychotic disorders such as schizophrenia (SCZ). The nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) is reported to be associated with cognitive function in nicotine-dependent populations and SCZ in non-smoking SCZ patients. Nevertheless, it is still not clear whether the CHRNA5 gene contributes to susceptibility to the cognitive deficits of SCZ without smoking. To further clarify the role of CHRNA5, we designed a two-stage, case-control study to examine the association between CHRNA5 and SCZ and its clinical features adjusted for smoking status in early-onset SCZ patients. A total of 15 tag single nucleotide polymorphisms (SNPs) on CHRNA5 were genotyped in the discovery stage, which included 485 early-onset SCZ patients and 1018 controls, and then, we replicated this association in a confirmatory population of 674 patients and 1886 controls. The rs16969968 SNP was identified as significantly associated with SCZ in both datasets. In addition, the severity of psychotic symptoms and cognitive deficits was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Wisconsin Card Sorting Test (WCST). The rs16969968 SNP was associated with psychotic symptoms in patients and with cognitive function in patients and controls. Our results show that rs16969968 on CHRNA5 is tightly linked to genetic susceptibility, psychotic symptoms and cognitive deficits in SCZ in an early-onset Chinese population, suggesting that CHRNA5 may play an important role in the etiology of SCZ.

Nicotinic acetylcholine receptor gene polymorphism is not associated with tobacco-related oral squamous cell carcinoma.

BACKGROUND: Nicotinic acetylcholine receptor is implicated in carcinogenesis indirectly through increasing nicotine dependence and directly through its impact on cell-cycle regulation. Functional polymorphism in nicotinic acetylcholine receptor alpha-5 subunit gene (CHRNA5 c.1192G>A; rs16969968) is associated with nicotine dependence and risk of lung cancer. AIM: The aim of this study was to evaluate the association of CHRNA5 c.1192G>A polymorphism with the risk of oral squamous cell carcinoma (OSCC). SETTINGS AND DESIGN: This was a rural teaching hospital-based case-control study. MATERIALS AND METHODS: A total of 100 histopathologically confirmed cases of OSCC patients and 100 age- and gender-matched healthy individuals were genotyped for CHRNA5 c.1192G>A polymorphism by polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies among case and control groups were compared by Chi-squared test (Fisher's exact). RESULTS: The frequency of CHRNA5 c.1192A allele was 22% in OSCC patients and 26% in control individuals. The difference in the distribution of alleles and genotypes between case and control groups was not significant (P > 0.05). CONCLUSIONS: CHRNA5 c.1192G>A polymorphism is not associated with the risk of developing OSCC.

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.