Study of Serotonin Transporters Gene in Sporadic Amyotrophic Lateral Sclerosis in French Population

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, invariably fatal neurological disease that attack the nerve cells and responsible for controlling voluntary muscles. The disease belongs to group of disorders known as motor neuron disease which are characterized by gradual degeneration and death of motor neurons. Serotonin is a neurotransmitter existing in both central nervous systems (CNS) and gastrointestinal tracts (GI) and regulates visceral sensation through a paracrine signaling pathway. Our objective was to study if there is a link between the 5-HTTLPR (Linked Polymorphism Region) allele of the serotonin transporter gene and the existence of pyramidal or extra-pyramidal rigidity in different subgroup of ALS patients. This gene has never been studied in ALS. We analyzed the functional polymorphism 5-HTTLPR of the SLC6A4 serotonin transporter gene in 209 patients with ALS and 214 control population of 214 individuals. All subjects were of French origin dating at least three generations. The DNA was extracted from blood cells. The analysis of polymorphism HTTLPR localized in the promoter of the gene of the transporter of the serotonin (SCL6A4) was performed after PCR in 100ng of DNA. The results are analyzed by agaros gel electrophoresis (2 %). We obtained tow bands LL genotype with 512pb or the short allele SS with 469pb. We found no significant differences in allele and genotype frequencies in this 5-HTTLPR polymorphism studied in the SLC6A4 gene of ALS patients versus control patients. However, further studies will be necessary to fully reject the implication of SLC6A4in SLA. Indeed the expression of this gene is regulated by epigenetic processes, and these may still be impaired in SLA. Moreover, effects on mRNA splicing, protein localization, and properties of 5-HTT could be possible mechanisms for influencing SLA risk.