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Medicina
Croatian Medical Association - Rijeka branch
ISSN: 0025-7729
Vol. 44, No. 1, 2008, pp. 49-59
Bioline Code: me08006
Full paper language: Croatian
Document type: Research Article
Document available free of charge

Medicina, Vol. 44, No. 1, 2008, pp. 49-59

 en The role of polymorphisms in genes for the cytosolic and calciumindependent phospholipase A2 in the reproductive fitness of men
Buretić-Tomljanović, Alena; Vlastelić, Ivan; Nadalin, Sergej & Badovinac, Anđelka Radojčić

Abstract

Aim: The role of PLA2 superfamily enzymes is indicated in the human testes, associated with disturbance of spermatogenesis, and with hormonal secretion from anterior pituitary. The aim of this study was to investigate the association between two polymorphisms (rs10798059 in the cytosolic PLA2 gene -PLA2G4A and rs4375 in the calcium-independent PLA2 gene-PLA2G6A) and clinical features of 96 oligoasthenospermic or asthenospermic men. Methods: Sixty five infertile men with idiopathic infertility were included in the study. Genetic analyses were performed using PCR-RFLP method while chi-square test, multiple stepwise regression and ANOVA were used in the statistical analyses.
Results: The frequencies of cPLA2 and iPLA2 genotypes and alleles were not significantly different between tested group and 59 control men. Multiple stepwise regression analysis showed a statistically significant association between both investigated polymorphisms and FSH serum level in 96 patients (P<0,05). Furthermore, iPLA2 polymorphism was significantly associated with sperm number and total serum testosterone level (in both cases P<0,05). Additional multiple stepwise regression analysis in 65 men with idiopathic infertility confirmed an association between iPLA2 (βFSH=0,504; P<0,0001) and cPLA2 (βFSH=0,322; P<0,01) polymorphisms and FSH means at a higher level of statistical significance. The same analysis also revealed an association between LH means and iPLA2 polymorphism (βLH=0,319; P<0,02). The genotype C/C of the iPLA2 polymorphism was associated with the highest mean FSH value (above the physiologic range) while the lowest mean was found in heterozygotes (T/C). According to iPLA2 genotype, LH means varied within the physiologic range but were distributed in the same manner as did FSH means.
Conclusions: The results suggest that investigated iPLA2 and cPLA2 polymorphisms might influence the exocytosis of gonadotropins from the anterior pituitary and/or testes function, thus modulating reproductive fitness in men

Keywords
genetic analysis, genetic polymorphisms, gonadotropins, male infertility, phospholipase A2, testosterone

 
 hr Utjecaj polimorfizama gena za citosolnu i o kalciju neovisnu fosfolipazu A2 na reproduktivnu sposobnost muškaraca
Buretić-Tomljanović, Alena; Vlastelić, Ivan; Nadalin, Sergej & Badovinac, Anđelka Radojčić


Cilj: Uloga enzima iz superobitelji fosfolipaza A2 indicirana je u testisima, povezano s poremećajem spermatogeneze, te u prednjem režnju hipofize, gdje sudjeluje u lučenju gonadotropnih hormona, prolaktina i ACTH. U radu se istražuje moguća povezanost dvaju polimorfizama, u genu za citosolnu PLA2 (PLA2G4A, rs10798059) i genu za o kalciju neovisnu PLA2 (PLA2G6A, rs4375), s kliničkim značajkama 96 muškaraca s oligoastenospermijom ili astenospermijom, od kojih je 65 imalo neplodnost nepoznata uzroka.
Metode: U genskoj analizi korištena je metoda PCR-RFLP, a u analizi rezultata χ2-test, stupnjevita regresijska analiza i ANOVA.
Rezultati: Učestalosti ispitanih genotipova i alela nisu značajno različite među ispitanicima i 59 kontrolnih muškaraca. Stupnjevita regresijska analiza pokazala je statistički značajnu povezanost oba polimorfizma s vrijednostima FSH u serumu ispitanika, te polimorfizma iPLA2 s brojem spermija i vrijednostima ukupnog testosterona na razini statističke značajnosti manje od 5%. Dodatna regresijska analiza u skupini 65 muškaraca s idiopatskom neplodnošću potvrdila je povezanost serumske vrijednosti FSH s polimorfizmima iPLA2 (βFSH=0,504; F=19,827; P<0,0001) i cPLA2 (βFSH=0,322; F=9,670; P<0,01), te serumske vrijednosti LH i polimorfizma iPLA2 (βLH=0,319; F=6,892; P<0,02) i to s većom statističkom vjerojatnošću. Genotip C/C iPLA2 polimorfizma udružen je s najvišom srednjom vrijednosti FSH u serumu (višom od fizioloških granica), dok su najniže srednje vrijednosti zabilježene u heterozigota (T/C). LH vrijednosti pokazuju isti uzorak raspodjele prema iPLA2 genotipu, ali je varijabilnost razine hormona unutar fizioloških granica.
Zaključak: Rezultati upućuju na to da bi navedeni polimorfizmi mogli, zasad nepoznatim mehanizmom, utjecati na proces lučenja gonadotropnih hormona iz prednjeg režnja hipofize i/ili na funkciju testisa, a time i na reproduktivnu sposobnost muškaraca.


fosfolipaza A2, genetička analiza, genski polimorfizmi, gonadotropni hormoni, neplodnost, testosteron

 
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