Association of the PTGS2 8473T>C polymorphism with depression and nausea in Iranian migraineurs

Migraine is a complex neurological disorder lacking reliable assessment methods. Non-steroidal anti-inflammatory drugs relieve migraine pain by inhibiting prostaglandin synthesis through COX-1 and COX-2 suppression. As COX-2 plays a key role in pain and inflammation, its modulation is vital in migraine therapy. We hypothesized that the COX-2 8473 T>C (rs5275) gene variant may be linked to migraine, depression, and nausea.

In this case-control study, genomic DNA from 100 migraine patients and 100 controls was analyzed for the COX-2 8473 T>C (rs5275) polymorphism using PCR-RFLP.

Statistical analysis revealed a significant association between the COX-2 8473 T>C variant and increased risk of migraine progression, depression, and nausea. The T+ genotype was more prevalent in controls than in patients (93% and 68% respectively; p < 0.0001), while the C+ genotype was more frequent in patients than controls (70% and 25% respectively; p < 0.001). Among migraineurs with depression, 75% carried the C+ genotype compared to 25% in controls (p < 0.001). Similarly, 76.1% of migraine patients with nausea had the C+ genotype, versus 25% of controls (p < 0.001).

The COX-2 8473 C+ genotype appears to increase the risk of migraine, depression, and nausea, while the T+ genotype may have a protective effect. This comparative genomics study highlights the potential role of the COX-2 8473 C+ genotype in migraine manifestation, though further research is needed to clarify its pathogenic involvement.