Association Study Between The LINGO Gene Family And Essential Tremor

Objective To explore whether the leucine-rich repeat and1g domain containing nogo receptor-interacting protein1gene(LINGO1) plays a role in Hunan Han patients with essential tremor (ET) susceptibility, we performed genetic analysis of coding region of the LINGO1gene, and analysedthe genotypeic and allelic distributions of these variants between the patients and the controls.Methods Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was conducted in genetic analysis of the LINGO1gene, and direct sequencing was performed to confirm the genotype of these variantsin the first100cases. And then the risk of these variants was evaluated between enlarged ET group (151cases including100cases from the first study) and sex, age and ethnicity matched nomal controls group (301cases) to increase statistical sensitivity.Results1. Four variants (rs2271398, rs2271397, a novel G>C transition ss491228439, and rs3743481) in the LINGO1gene were identified by the first step PCR-SSCP and sequencing analysis in100cases. All the4variants in the LINGO1gene were synonymous mutation and these were no predicted amino acid change or splicing site change.2. In our extended study of these4variants (rs2271398, rs2271397, ss491228439and rs3743481) in151ET patients and301age, gender and ethnicity matched normal controls, no statistically significant differences in genotypeic and allelic distributions between the patients and the controls were found (All P>0.05). However, further sex-stratified analysis revealed that the C allelle of rs2271397and ss491228439contributed the risk of ET (P=0.017, OR=2.139,95%CI1.135-4.030for rs2271397and P=0.038, OR=1.812,95%CI1.027-3.194for ss491228439, respectively), and thehaplotype (A465-C474-C714) was associated with increased risk of female patients with ET (P=0.041, OR=1.800,95%CI1.020～3.178) and the wild-type haplotype (G465-T474-G714) may play the opposite role in this disorder (P=0.023, OR=0.484,95%CI0.256～0.915).Conclusions The LINGO1variants may be associated with ET in Han female ET patientsfrom Hunan province. Objective To explore whether the leucine-rich repeat and1g domain containing nogo receptor-interacting protein4gene (LINGO4) plays a role in Hunan Han patients with essential tremor (ET) susceptibility, we performed genetic analysis of coding region of the LINGO4gene.Methods Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was conducted in genetic analysis of the LINGO4gene, and direct sequencing was performed to confirm the genotype of these variantsin the first100cases. And then the risk of these variants was evaluated between enlarged ET group (150cases including100cases from the first study) and sex, age and ethnicity matched nomal controls (300cases)to increase statistical sensitivity. Bioinformatics prediction software program Mutation Taster was used to predict disease risk of the missense mutation.Results1. Two variants (rs61746299and rs1521179) in the LINGO4gene were identified by the first step PCR-SSCP and sequencing analysis in100cases. Rs61746299is a coding variant, predicted to lead to alter threonine into serine at amino acid position444(Thr444Ser). Whereas rs1521179, located12bp downstream to the end of coding region, with no slicing site change.2. In our extended study of these2variants in150ET patients and300age, gender and ethnicity matched normal controls, no statistically significant differences in genotypeic and allelic distributions between the patients and the controls were found(All P>0.05). And further stratified analysis revealed no statistically significant difference in family ET group, sporadic ET group, early-onset ET group and late-onset ET group (All P>0.05).3. Bioinformatics prediction software program Mutation Taster predictes the substitution of a threonine for a serine (rs61746299) to be polymorphism.Conclusions The LINGO4gene may not the disease-causing gene or the susceptibility gene of ET patients from Hunan province.