Effect of Genetic Variation in Kv1.3 on Olfactory Function

Background: Olfactory function is reduced in aged humans and diabetes mellitus patients. However, little is known about the pathogenic mechanisms leading to olfactory dysfunction. Recently, it has been shown that the voltage-gated potassium channel Kv1.3 is regulated by insulin and is highly expressed in the olfactory bulb. Furthermore, the function of this channel is associated with olfaction in mice and with glucose metabolism in mice and men. We therefore hypothesized that a functionally relevant polymorphism in Kv1.3 might alter olfactory function.

Methods: We investigated a group of 94 healthy subjects (male: n = 58, female: n = 36) for olfactory function and genotyped them for rs2821557 in the human Kv1.3 gene. Olfactory function was tested using standardised sniffing sticks, and parameters of glucose metabolism were assessed.

Results: We found a significant olfactory impairment in male homozygous carriers of the Kv1.3 polymorphism rs2821557 (recessive model, p = 0.018, adjusted for age) that could not be determined in female subjects due to the very small number of homozygous minor allele carriers (n = 1). In addition, we found a significant correlation of olfactory dysfunction with higher HbA1c and fasting plasma glucose (p = 0.004 and p = 0.001, both adjusted for age). We also found a loss of olfactory function with age (p = 0.006). Gender, body mass index and insulin sensitivity did not alter smelling function.

Conclusions: The presence of genetic variation in Kv1.3 is associated with decreased olfactory function in healthy subjects. As olfactory function, glucose metabolism and genetic variation in Kv1.3 seem to be associated, further studies are needed to clarify the underlying mechanisms.