The Thr105Ile Variant (rs11558538) of the Histamine N-methyltransferase Gene may be associated with Reduced Risk of Parkinson Disease: A Meta-analysis

Background: Previous studies have reported conflicting results regarding the potential association between the risk of Parkinson's disease (PD) and the single nucleotide polymorphism, rs11558538 (Thr105Ile), in the histamine N-methyltransferase (HNMT) gene. We performed a systematic review and meta-analysis to improve our understanding of the association between them. Methods: We systematically searched several online databases to identify relevant studies regarding the association between rs11558538 and PD. We extracted data on the frequencies of genotypes (Thr/Thr, Thr/Ile, and Ile/Ile) and alleles (Thr and Ile) at the rs11558538 locus in patients with PD and healthy controls. Associations between genotype and PD risk were assessed in terms of odds ratios (OR) and 95% confidence intervals (CI). Results: The final meta-analysis included six case-control studies and data from the International Parkinson's Disease Genomics Consortium (IPDGC) data base on the association between HNMT rs11558538 and PD, involving 22,855 patients and 65,367 controls. Among the studies, substantial heterogeneity was observed (I² = 84.42 for genotype and I² = 73.39 for allele). Both the Ile (log OR: -0.31; 95% CI: -0.5 to -0.12; p < 0.001) and Thr/Ile+Ile genotypes (log OR: -0.32; 95% CI: -0.55 to -0.08; p < 0.001) were associated with a decreased risk of sporadic PD across all study populations. Subgroup analysis showed the protective effect of Thr/Ile+Ile genotypes in non-Chinese cohorts (log OR: -0.66; 95% CI: -0.67 to -0.04; p < 0.001) but not in Chinese cohorts (log OR: -0.26; 95% CI: -0.63 to 0.11; p = 0.13). Conclusion: Our findings suggest that the HNMT rs11558538T polymorphism may protect against PD, particularly in patients from the United States and Europe.