Genetic correlations between migraine and carpal tunnel syndrome.

BACKGROUND: Surgical deactivation of extracranial nerve trigger sites is now well-established as an effective treatment for migraine headache. Parallels have been drawn to median nerve decompression for carpal tunnel syndrome (CTS), and two previous studies have demonstrated an association between migraine and CTS. We sought to: (1) substantiate these findings in a considerably larger UK cohort, and; (2) investigate potential genetic associations between the two disorders. METHODS: Nested case-control studies were conducted in the UK Biobank cohort of 401,656 individuals. Odds ratios were calculated for the association between migraine and CTS in the overall cohort and sex-stratified subsets. Genetic correlation between migraine and CTS was interrogated by linkage disequilibrium score regression (LDSC), leveraging data from published genome-wide association studies. Regions of genetic overlap were identified by Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC). RESULTS: Migraine and CTS show a significant epidemiological association within UK Biobank (OR=1.14, 95% CI: 1.04-1.25, p=0.0058), which is specific to females (OR=1.15; 95% CI: 1.04-1.28, p=0.0057) and not males (OR=1.07; 95% CI: 0.82-1.40, p=0.61). Genetic analysis demonstrated a significant positive genetic correlation between the two disorders (rg=0.13, p=0.0039), and implicated the TRIM32 locus on chromosome 9 as a region of genetic overlap. CONCLUSIONS: This study replicates past reports of an epidemiological association between CTS and migraine, albeit in females only. This association is underpinned by a genetic correlation, with shared genetic susceptibility at the TRIM32 locus. Our data adds credibility to the notion that an element of entrapment neuropathy underlies migraine pathophysiology.

Increase in NF-kappaB binding affinity of the variant C allele of the toll-like receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease.

Colonization of the gastric mucosa by Helicobacter pylori can lead to serious clinical outcomes, including gastric cancer. Toll-like receptors (TLRs) play an important role in the host response to H. pylori through the recognition of pathogen-associated molecular patterns. TLR9, in particular, is partly responsible for initiating bacterial induced immunity by binding unmethylated CpG-DNA, which is abundant in bacteria. A well-documented single nucleotide polymorphism (SNP) within the TLR9 promoter (TLR9 -1237T/C), is associated with a variety of inflammatory disorders, including allergic asthma, inflammatory bowel disease, and atopy. Analysis of the TLR9 promoter gene sequence has shown that carriage of the variant "C" allele at position -1237 creates a potential NF-kappaB binding site that would theoretically increase the transcriptional activity of the gene. In this study, we report that the TLR9 -1237 C allele was significantly associated with the development of H. pylori-induced premalignant gastric changes. Functional analysis of the SNP, supporting the data generated from the genetic association study, showed that carriage of the C allele increased TLR9 transcriptional activity driven mainly by activation of NF-kappaB. Collectively, these findings confirm that the TLR9 -1237T/C polymorphism is a risk factor for the development of H. pylori-induced premalignant gastric changes and provide a plausible mechanistic explanation.