Sex matters! Interactions of sex and polymorphisms of a cholinergic receptor gene (CHRNA5) modulate response speed

Abstract

Acetylcholine influences the speed of information processing. We examined the effect of the rs3841324 polymorphism (L/S) and the rs16969968 (G/A) polymorphism on response speed in the Stroop task and the Negative priming task. These polymorphisms are located in the gene that encodes the nicotinic acetylcholine receptor α5-subunit (CHRNA5). Male carriers of the rs3841324 S/S genotype and the rs16969968 G/G genotype were faster than male carriers of at least one L allele or one A allele. In contrast, female carriers of the rs3841324 S/S genotype and the rs16969968 G/G genotype were slower than female carriers of at least one L allele or one A allele. These results indicate that the minor alleles of both polymorphisms modulate response speed in a sex-dependent, diametrically opposed manner.

Sex, ADHD symptoms, and CHRNA5 genotype influence reaction time but not response inhibition

“…The aim of this study was to replicate some findings of Crosbie et al () and Schneider et al (), and extend them toward a possible modulation of indices of the Stop Signal Task (SST) by ADHD symptomatology, SNPs of CHRNA5 as a representative candidate gene of the cholinergic system and sex differences. The SST (Logan, Cowan, & Davis, ) was invented to investigate response inhibition, and can also be used to measure response time in a forced‐choice task as well as response time variability.…”

“…In humans, association studies with single nucleotide polymorphisms (SNPs) of the encoding gene CHRNA5 and cognitive enhancement (Rigbi et al, ; Schuch et al, ; Winterer et al, ), impulsivity (Criado, Gizer, Edenberg, & Ehlers, ; Stephens et al, ), and response inhibition (Rigbi et al, ; Schneider, ) have been performed. One of the functionally characterized polymorphisms, the non‐synonymous SNP rs16969968 G/A, has been selected in this study due to the properties of the G allele to increase receptor affinity (Bierut et al, ) and its association with increased reaction time in males (Schneider, Hüle, Schote, Meyer, & Frings, ). Furthermore, rs16969968 is in high linkage disequilibrium with rs3841324, a 22 base pair insertion/deletion variant in the promoter of CHRNA5 .…”

“…To date, this length polymorphism has been investigated only in few association studies that focus on tobacco use, cancer or cognitive flexibility (Wei et al, ; Zhang, Kranzler, Poling, & Gelernter, ; Zheng et al, ) but it directly affects CHRNA5 mRNA expression (Wang, Cruchaga, et al, ; Wei et al, ). Carriers of the rs3841324 S‐allele showed lower transcription rates of CHRNA5 , which might lead to decreased ligand sensitivity and probably to lower reaction times observed in respective tasks (Schneider et al, ). Interestingly, this effect was found in males only, while female participants showed a diametrically opposed effect of genotype on reaction time (Schneider et al, ).…”

“…Carriers of the rs3841324 S‐allele showed lower transcription rates of CHRNA5 , which might lead to decreased ligand sensitivity and probably to lower reaction times observed in respective tasks (Schneider et al, ). Interestingly, this effect was found in males only, while female participants showed a diametrically opposed effect of genotype on reaction time (Schneider et al, ). Furthermore, sex‐dependent differences of nACh receptor actions have been found in rodents (Koylu, Demirgören, London, & Pöğün, ), and more recently in humans (Wei et al, ; Xie et al, ).…”

Individual response speed is modulated by variants of the gene encoding the alpha 4 sub-unit of the nicotinic acetylcholine receptor (CHRNA4)

“…This sample is part of a larger sample that has also been analyzed in regard to several polymorphisms (see[45,46])3 Recently,[47] have reported on the low extent of genetic heterogeneity in German samples. In their study, only a slight north-south gradient was detectible, though this difference was still several times smaller than those between samples drawn in Germany and samples in other Germanic populations, accounting for far less than 5 % of the total variance.…”