Estudio de los polimorfismos de las acuaporinas 1 y 4, leptina sérica y fístula espontánea de líquido cefalorraquídeo en la hipertensión intracraneal idiopática

Laburpena

Introduction: Idiopathic intracranial hypertension is a disease of the central nervous system characterized by symptoms and signs derived from increased intracranial pressure in the absence of space-occupying lesions or hydrocephalus. It is characteristic of young, obese women of childbearing age. Its pathophysiology is still not clear. There are several theories, including an increase in leptin levels, a hormone responsible for weight and appetite regulation, and alterations in aquaporins 1 and 4, integral membrane proteins responsible for the movement of water in the brain and involved in the formation of cerebral edema. The clinical presentation is highly variable, which can make diagnosis difficult. In addition to the classic symptoms of throbbing headache that worsens with Valsalva maneuvers, fleeting amaurosis, campimetric visual defects, diplopia, and pulsatile tinnitus, spontaneous cerebrospinal fluid fistula is considered in many publications as one more manifestation of the disease. Material and methods: A prospective descriptive study of 72 patients with idiopathic intracranial hypertension was carried out. The polymorphisms of aquaporins 1 (rs1049305 and rs10244884) and 4 (rs3763043, rs3763040 and rs2075575) and the serum levels of leptin were determined from a blood sample from each patient. For each of the patients, the genotypic distribution, allelic frequencies and allelic dominance models were determined. As a control group, samples of the general healthy population from the bank of the Institute of Molecular Biology and Genetics (IBGM) were used. A statistical study was performed using the chi-square (χ2) test, considering p≤0.05 statistically significant. Results: Significant differences were found in the rs3763040 polymorphism study of aquaporin 4 in the genotypic distribution with p=0.048, in the allelic frequency with p=0.0341 and in allelic dominance (GG vs GA+AA) with a p=0.0309. No significant differences were found in the study of aquaporin polymorphisms 1 (rs1049305 and rs10244884) and 4 (rs3763043 and rs2075575). The study of serum leptin showed significant differences (p=0.0014) in women with normal BMI where leptin is elevated, unlike women with BMI of overweight and obesity, which was not statistically significant. Significant differences were also found when comparing both groups of men and women with normal BMI vs. overweight and obese BMI (p=0.0015). In relation to CSF fistula, 17.39% of the patients presented CSF fistula, 33.3% of the patients were men and 66.7% women, and no significant differences were found between the polymorphisms studied and spontaneous CSF fistula. Conclusion: The finding of the rs3763040 polymorphism as a statistically significant result can be interpreted either as an alteration that favors the disease, or as a normal variant. The existence of clinical data and changes in serum leptin not related to this polymorphism leads us to believe that it is a multifactorial disease.