Nicotinamide-N-Methyltransferase gene rs694539 variant and migraine risk.

BACKGROUND: Migraine is a common neurovascular disorder affecting 10 to 20 % of the world population usually subdivided into migraine with auro (MA) and migraine without auro (MO). Homocysteine is involved in the pathophysiology of a number of neurological disorders. Elevated levels of homocysteine in the plasma is produced by the MTHFR gene rs 1801133 and rs 1801131 variants as well as the NNMT gene rs 694539 variant. METHODS: With the polymerase chain reaction-restriction fragment length polymorphism method developed recently in our laboratory, we were able to show an association between the NNMT gene rs694539 variant and migraine for the first time. RESULTS: Here we report the association of the Nicotinamide-N-methyltransferase gene (NNMT) rs694539 variant with migraine in a case-control study of 433 patients with migraine and 229 healthy controls (χ2 = 6.076, P = 0.048). After stratification, we were able only to show an association between the NNMT gene rs694539 variant and female patients with migraine on the genotype and allelic levels. However there was no association in male patients with migraine (χ2 = 1.054, P = 0.590). CONCLUSIONS: Consequently our results clearly indicate that the NNMT gene rs694539 variant is a genetic risk factor for migraine.

Association of Nicotinamide-N-Methyltransferase Gene rs694539 Variant with Epilepsy.

Here, we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with epilepsy in a case-control study of 215 patients with epilepsy and 239 healthy controls (χ (2) = 11.641, P = 0.003). The individuals with the GG genotype revealed protection against epilepsy (χ (2) = 5.866, P = 0.015, OR = 0.623, 95 % CI = 0.425-0.915), whereas the individuals with the AA genotype showed statistically significant increased risk for epilepsy (χ (2) = 8.676, P = 0.003, OR = 5.479, 95 % CI = 1.553-19.337). In addition, the G allele was protective against epilepsy (χ (2) = 8.676, P = 0.003, OR = 0.183, 95 % CI = 0.052-0.644); on the contrary, the A allele was a genetic risk factor for epilepsy (χ (2) = 5.866, P = 0.015, OR = 1.604, 95 % CI = 1.093-2.354). Stratification analysis revealed that the association was statistically significant in male patients with epilepsy (χ (2) = 6.682, P = 0.035). However, the statistical power was only 0.33 in female patients with epilepsy (χ (2) = 5.275, P = 0.072). This finding, for the first time, suggests the involvement of the NNMT gene rs694539 variant in the etiology of epilepsy.