We sought to determine the prevalence of RLS in CADASIL patients with different Notch3 mutations, both with and without migraine as a clinical feature.
Additional molecular insight into the pathophysiology of migraine may come from other monogenic syndromes (for instance cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is caused by NOTCH3 mutations), in which migraine is prominent.
Notch3 genotypes as well as allele frequencies did not differ in migraine patients compared to controls, even adjusting for the presence of possible confounds.
We report a patient with a condition strongly suggestive of CADASIL (migraine, stroke, and white matter abnormalities), except that this patient did not have any first-degree relatives with similar symptoms.
For further replicate these findings, we selected two SNPs; rs2651899 on chromosome 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population.
The large number of detected loci, chief among them TRPM8, PRDM16, and LRP1, have enabled a number of in silico analyses, which have shed light on the functional and tissue-level aspects of the common risk variants for migraine, including evidence for involvement of both vascular and neuronal mechanisms.
Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus.
We report significant influence of rs1835740, LRP1 rs11172113 and PRDM16rs2651899 polymorphisms on migraine susceptibility in the North Indian population.
To further replicate the GWAS findings, we investigated the 3 variants rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8), and rs11172113 (12q13.3, LRP1) for their association with migraine in the Chinese Han population.
We identified the minor allele of rs2651899 located in PRDM16 to be associated with migraine (P = .005, odds ratio = 1.382, 95% confidence interval = 1.100-1.736), the association remain significant after Bonferroni correction.
Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO.
We report significant influence of rs1835740, LRP1rs11172113 and PRDM16 rs2651899 polymorphisms on migraine susceptibility in the North Indian population.