engleski

MAO-A and MAO-B genes polymorphisms in migrainous patients

Migraine is a neurovascular disorder of still insufficiently understood etiology. It is viewed as a polygenic multifactorial disease whose genetics is under intensive research. In search for susceptibility genes implicated in this complex disorder, we have proposed two candidate genes encoding monoamine oxidases A and B (MAO-A and -B), isoenzymes that catalyze the oxidative deamination of biogenic amines, including monoamine neurotransmitters serotonin and norepinephrine. These two enzymes are of interest because they have a role in regulating serotonin and norepinephrine in the central nervous system. We have investigated possible association between one functional polymorphism in each gene with two common types of migraine: migraine without and migraine with aura. We have tested variable number of tandem repeats (VNTR) polymorphism in MAO-A gene promoter and A/G dimorphism in intron 13 of MAO-B gene. The sample consisted of 110 migrainous patients (80 women and 30 men): 80 suffering from migraine without aura and 30 from migraine with aura. The control sample comprised of 150 healthy volunteers (100 women and 50 men). Promoter VNTR was detected by amplifying the region of interest from isolated genomic DNA with polymerase chain reaction (PCR) and synthesized products were genotyped on 10% polyacrilamide gel. A/G dimorphism was genotyped using allele-specific oligonucleotide PCR (ASO-PCR) and presence or absence of products was detected on 1, 6% agarose gel. We have found statistically significant association (P=0, 0423) between the shorter variant of MAO-A VNTR allelic form with migraine without aura in male patients. In the case of migraine with aura we have found no association. The same is true for both types of migraine in respect to MAO-B gene A/G dimorphism. Results of this association study suggest minimal association of MAO-A gene promoter polymorphism with migraine without aura. This tendency toward higher frequency of shorter allelic variant, responsible for lower MAO-A activity, could be an indication of altered monoamine neurotransmitter levels in brainstem nuclei. It raises the possibility that levels of serotonin and norepinephrine are higher than normal thus leading to enhanced neuronal activity in the brainstem and providing an argument for the "central generator" theory of migraine ; however, the finding should be confirmed on a larger sample.

monoamine oxidase; gene polymorphism; migraine

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