Endothelin Receptor A –231 G>A Polymorphism: No Linkage to Primary Pediatric Headache


  • Veronica Lisi PhD,

  • Greta Garbo BS,

  • PierAntonio Battistella MD,

  • Flavia Miccichè BS,

  • Anna Stecca BS,

  • Salvatore Terrazzino PhD,

  • Malida Franzoi MD,

  • Elisa Tripoli MD,

  • Alberta Leon PhD,

  • Maurizio Clementi MD

  • From the Research and Innovation (R&I) Company, Padova, Italy (Drs. Lisi, Terrazzino, Leon, and Miccichè, Stecca); Department of Pediatrics, University of Padua, Italy (Garbo, Drs. Battistella, Franzoi, Tripoli, Clementi); and IRCCS St. Camillo Hospital, Venice, Italy (Dr. Leon).

Address all correspondence to Dr. Veronica Lisi, Research and Innovation Company (R&I) Via Svizzera 16, 35127 Padova, Italy.


Objective.—To assess whether the biallelic –231 G>A polymorphism of the endothelin type A receptor (EDNRA) gene, previously shown to be a marker of increased risk for developing migraine, has a role in the susceptibility to primary pediatric headache.

Background.—Several studies suggest that endothelin has a role in migraine. A recent association study has shown that the biallelic –231 G>A polymorphism of the EDNRA gene is associated to migraine in an elderly population.

Methods.—A total of 126 consecutive unrelated pediatric patients affected by primary headache, classified according to the International Headache Society criteria in migraine (migraine with aura, n = 3; migraine without aura, n = 80), and tension-type headache (episodic tension-type headache, n = 36; chronic tension-type headache, n = 7) patients, were recruited to the study. Sixty-seven healthy blood donors were used as a control group. Genomic DNA was extracted from buccal swabs or blood samples and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the above-mentioned polymorphism. Allele and genotype frequencies for primary headache patients were analyzed in comparison with the control group.

Results.—No significant differences were found in the distribution of the EDNRA –231 G>A polymorphic variant when considering both genotype (migraine χ2= 2.78, P= .25; tension-type headache χ2= 3.58, P= .17) and allelic frequencies (migraine χ2= 1.48, P= .22; tension-type headache χ2= 0.39, P= .56). Furthermore, no significant genotype-related difference was found in relation to clinical features, such as age at onset, frequency, and length of the attacks.

Conclusions.—Our study shows that the –231 G>A polymorphism in the EDNRA gene is neither associated with primary juvenile headache nor significantly correlated with main clinical features characteristic of the headache pathology in pediatric settings.