Naslov
Impact of PLA2G4A and PTGS2 gene polymorphisms and red blood cell PUFAs deficit on niacin skin-flush response in patients with schizophrenia

Autori
Nadalin, Sergej ; Giacometti, Jasminka ; Jonovska, Suzana ; Buretić-Tomljanović, Alena

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the FEBS3+ Meeting From Molecules to life and back / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka - : Fintrade & Tours, 2012, 97-97

Skup
FEBS 3+ Meeting From Molecule to Life and Back

Mjesto i datum
Opatija, Hrvatska, 13.06.2012. - 16.06.2012

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
schizophrenia; niacin skin flush test; PLA2G4A polymorphism; PTGS2 polymorphism; red blood cell membranes; essential polyunsaturated fatty acids

Sažetak
OBJECTIVE: Attenuated niacin skin-flush response in schizophrenia marks cytosolic phospholipase A2/cyclooxygenase-2 (cPLA2/COX-2) cascade abnormalities and has been proposed as an endophenotype in this illness. We investigated whether, and to what extent, niacin flush response in patients with schizophrenia, could be related to polymorphisms in genes of the cPLA2/COX-2 cascade. We also tested possible correlation between niacin response and fatty acid (FA) profile of their red blood cells (RBC). METHODS: Patches containing 0.1M, 0.01M, 0.001M and 0.0001M of niacin solution were kept for 5 minutes on the forearm skin in 79 patients and 80 controls. Visual evaluation of flushing rated from zero to three was done in 5-minute intervals by two independent raters. The genotyping of BanI polymorphism of the PLA2G4A gene (cPLA2) and A/G variant (rs689466) of the PTGS2 gene (COX-2) of the subjects that underwent niacin sensitivity testing was revealed by PCR-RFLP analysis. Total RBC lipids were extracted, converted into FA methyl esters and further analyzed by gas chromatography. We determined the relative amount of different saturated FAs (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) from n-3 and n-6 series. We introduced several indices and ratios into analysis. RESULTS: Both polymorphisms diminished niacin flushing to a small, although significant extent (1.7% and 1.8% ; P<0.01) in the patient group. Analysis of the RBCs' FAs content revealed that double bond index/peroxidizability index (DBI/PI) ratio accounted for 44.6% - 47.3% of flushing variability (at 0.01M niacin concentration and two time-intervals). Negative and high correlation between niacin response and DBI/PI ratio (1 = -0.69 and 2 = -0.67) indicated an association between decreased relative RBC content of, especially, long-chain PUFAs (LC-PUFAs) and attenuated niacin response in patients. Significant decreases in relative content of eicosapentaenoic acid, docosahexaenoic acid, total PUFAs, linoleic acid, DBI, PI, and several ratios (PUFAs/SFAs, PUFAs/MUFAs), and significant increase in the relative SFA content contributed to this finding (P<0.01 or P<0.001). CONCLUSIONS: Both polymorphisms as well as deficits in RBC LC-PUFAs significantly contributed to blunted niacin response in patients with schizophrenia. FA profile of their RBC membranes affected niacin flushing substantially while PLA2 and COX-2 gene variations affected skin response to a negligible extent.

Izvorni jezik
Engleski

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