Respiratory sinus arrhythmia and serotonin transporter promoter gene polymorphisms: Taking a triallelic approach makes a difference

It has been recently reported in Psychophysiology that carriers of the short allele of an insertion/deletion (ins/del) functional polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene may display decreased resting respiratory sinus arrhythmia (RSA). However, this region hosts another functionally connected single-nucleotide polymorphism (rs25531), which should also be genotyped in order to correctly categorize the low- and high-expressing alleles of 5-HTTLPR. The present study investigated resting RSA in an ethnically homogenous sample (N = 143) of participants genotyped for both the ins/del and rs25531 polymorphisms in 5-HTTLPR. In contrast with the biallelic genotypes, based only on the ins/del alleles, the triallelic 5-HTTLPR genotypes (i.e., including rs25531) showed no association with resting RSA. Taking a triallelic approach to 5-HTTLPR is thus necessary in order to avoid false positive results.