Objective: We studied the involvement of LINGO1 and LINGO2 in Russian patients with ET and PD.

Background: Genetics of ET is unclear. Three candidate loci were mapped on different chromosomes, and results of several genome-wide association studies remain controversial. Some variants of LINGO1 and its paralog LINGO2 genes have recently been associated with an increased risk of developing ET and PD, the findings supporting the existence of genetic link between ET and PD and demanding further studies.

Methods: We sequenced coding regions of LINGO1 (2 exons) and LINGO2 (1 exon) in Russian patients with ET (n=56) and PD (n=39). With multiplex PCR we investigated six selected candidate SNPs: rs9652490 and rs11856808 in LINGO1, and rs1412229, rs10968280, rs10812774 and rs7033345 in LINGO2.

Results: Sequencing analysis in ET and PD patients detected five known SNPs in the LINGO1 coding region (rs3743481, rs61737308, rs2271396, rs2271397 and rs2271398), as well as one novel coding variant (g.27949151G>A) in LINGO2. Minor allele frequency (MAF) of rs3743481 was significantly higher in PD group than in ET group (0.538 vs 0.312, p=0.002). We identified the rare SNP rs61737308 (global MAF 0.0034) in two ET cases, both with early-onset tremor and positive family history of ET/PD. The novel variant g.27949151G>A (Arg507Cys) in LINGO2 was detected in a sporadic ET case with early onset. The amino acid substitution Arg507Cys was considered as ‘tolerated’ with SIFT database and ‘possibly damaging’ with PolyPhen2. Among SNPs genotyped with multiplex PCR, only rs9652490 in LINGO1 had significantly higher MAF in ET than in PD (MAF 0.232 vs 0.103, p=0.022), whereas allele frequencies of other SNPs did not differ between groups.

Conclusions: We presented the first preliminary results of an analysis of ET-associated genes in a Russian cohort of patients with ET and PD. We identified several LINGO1 variants with different frequencies in ET and PD and one novel LINGO2 variant in ET case. These findings should be validated in further studies. This work was supported by the Ministry of Science and Education of Russia; UID number RFMEFI60714X0094.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-lingo1-and-lingo2-genes-in-essential-tremor-and-parkinsons-disease/