Genetic analysis of the leucine-rich repeat and lg domain containing Nogo receptor-interacting protein 1 gene in essential tremor.

Variants in the leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1 gene (LINGO1) have been identified to be associated with the increased risk of essential tremor (ET), especially among Caucasians. To explore whether the LINGO1 gene plays a role in ET susceptibility, we performed a systematic genetic analysis of the coding region in the LINGO1 gene. Four nucleotide variants have been genotyped, including three known variants (rs2271398, rs2271397, and rs3743481), and a novel G → C transition (ss491228439). Extended analysis showed no significant difference in genotypic and allelic distributions between 151 patients and 301 control subjects for these four variants (all P > 0.05). However, further sex-stratified analysis revealed that the C allele of rs2271397 and ss491228439 contributed the risk of ET in female (P = 0.017, OR = 2.139, 95 % CI 1.135 ~ 4.030 for rs2271397 and P = 0.038, OR = 1.812, 95 % CI 1.027 ~ 3.194 for ss491228439). Haplotype analysis indicated that A465-C474-C714 haplotype was significantly associated with increased risk of ET in female (P = 0.041, OR = 1.800, 95 % CI 1.020 ~ 3.178). Our results indicate that the LINGO1 variants are associated with ET in Chinese Han female patients.