Koncentracija serotonina u trombocitima i polimorfizam serotoninskoga transportera u bolesnika sa Sjögrenovim sindromom

Šarac, Helena (2013) Koncentracija serotonina u trombocitima i polimorfizam serotoninskoga transportera u bolesnika sa Sjögrenovim sindromom. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Platelet serotonin level (PSL) is decreased in all examined inflammatory rheumatic disorders such as rheumatoid arthritis (RA), systemic lupus erythematodes (SLE), systemic sclerosis (SSc) and mixed connective tissue disorders (MCTD). The main goal of this study was to examine PSL main polymorphisms of serotonin transporter gene, 5-HTTLPR, rs25531 and 5-HTTin2VNTR to determine their potential association with depression and fatigue in patients with primary Sjögren's syndrome (pSS). Special goal in this study was to explore the frequency of signal hyperintensities (SH) of the brain in patients with primary Sjogren's syndrome who suffered frequent episodic tensio-type headache (FETTH) enough to sustain brain MRI, and association between SH and PSL. Clear difference between pSS patients and healthy controls was found, with PSL values being significantly lower in patient groups. Decreased PSL in Sjogrens' group, not in control group, is strongly influenced by the „low expressing“genotype s/s 5-HTTin2VNTR, indicating the important role of interaction gene x environment (G x E) on disease fenotypes, whereas genetic effects are potentially facilitated by environmental factors. PSL has strongly influenced on depression and fatigue in Sjogrens' patients, which suggests that PSL could be used as biomarker of the depression and fatigue in these patients. These results support a biopsychosocial model od pSS in which 5-HTT genotypes modifies risk for depression and fatigue. Long term, practiotioners may individualize treatment of pSS patients with depression and fatigue by sing PSL and 5-HTT genotype as two valuable parameters. Furthermore, the current study demonstrated that signal hyperintensities (SH) on brain MRI are more common in specific region of the brain of Sjögren's patients with frequent episodic tension-type headache (FETTH) than in age-matched controls with FETTH, indicating more widespread cerebral vasculopathy in Sjögren's group. Brain MRI represents a sensitive screening tool for detection of SH in pSS patients with FETTH. Association between PSL and periventricular lesions in this study is in line with hypothesis of interrelation between increased platelet serotonin release and pathophysiology of brain tissue damage in specific region of the brain in pSS patient with FETTH.

Abstract in Croatian

Koncentracija trombocitnog serotonina (engl. platelet serotonin level, PSL) je snižena u svim, do sada ispitivanim upalnim reumatskim bolestima kao što su reumatoidni artritis (RA), sistemski lupus (SLE), sistemska skleroza (SSc) i miješana bolest vezivnog tkiva (MCTD). Polazeći od pretpostavke da je PSL snižena i u primarnom Sjogrenovom sindromu (pSS), cilj ove studije bio je odrediti PSL i istražiti polimorfizme gena za serotoninski transporter (5-HTT); 5-HTTLPR, rs25531 i 5-HTTin2VNTR, utvrditi međusobnu povezanost između PSL i 5-HTT polimorfizama i njihov mogući utjecaj na depresiju i umor u bolesnika s pSS. Poseban cilj bio je i ispitati učestalost hiperintenziteta bijele tvari mozga u bolesnika s pSS s učestalom epizodičkom tenzijskom glavoboljom i njihovu moguću povezanost s PSL. Utvrdili smo jasnu razliku u PSL između bolesnika sa Sjogrenovim sindromom u odnosu na zdrave kontrole, pri čemu je PSL bila statistički značajno snižena u bolesnika s pSS. PSL je bio značajno niži u bolesnika s pSS nositelja s/s genotipa na intronu, 5-HTTin2VNTR u odnosu na kontole nositelje istog genotipa, što pruža snažne dokaze o ulozi interakcije geni x okoliš (G x E) u nastanku specifičnih fenotipova, gdje na gensku ekspresiju utječu vanjski čimbenici, pojačavajući njihovu aktivnost. PSL je značajno povezan s nastankom depresije i u mora u bolesnika s pSS, što upućuje na činjenicu da bi se PSL mogao koristiti kao važan biomarker depresije i umora u oboljelih od pSS. Ovi rezultati podupiru bipsihosocijalni model u pSS, pri čemu polimorfizmi gena za 5-HTT modificiraju rizik za nastanak depresije i umora u bolesnika s pSS. Dugoročno, PSl i polimorfizmi 5-HTT mogu se koristiti kao važni klinički parametri u individualizaciji terapije bolesnika s pSS sa simptomima depresije i umora. Ovim istraživanjem dokazali smo veću učestalost hiperintenziteta bijele tvari mozga u oboljelih of pSS koji imaju učestale epizodičke tenzijske glavobolje u odnosu na kontrole koji nemaju pSS, ali imaju isti tip glavobolja. Ovi podaci upućuju na opsežniju cerebralnu vaskulopatiju u grupi bolesnika sa Sjögrenovim sindromom, a MRI mozga je kao neuroradiološka metoda dovoljno osjetljiva u otkrivanju lezija bijele tvari mozga. Povezanost trombocitnog serotonina i periventrikularnih lezija u ovoj studiji je u skladu s hipotezom o međuzavisnosti pojačanog otpuštanja serotonina iz trombocita i patofiziologije oštećenja moždane tvari u bolesnika s pSS.

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