Title Varijabilnost gena matriks metaloproteinaza i tkivnih inhibitora metaloproteinaza u parova s ponavljajućim spontanim pobačajima nepoznate etiologije : doktorski rad Title (english) Variation of the matrix metalloproteinase and tissue inhibitors of metalloproteinase genes in couples with recurrent spontaneous abortion of unknown etiology : doctoral thesis Author Nina Pereza Mentor Saša Ostojić (mentor)Committee member Elvira Mustać (predsjednik povjerenstva)Committee member Marija Heffer (član povjerenstva)Committee member Oleg Petrović (član povjerenstva)Committee member Saša Ostojić (član povjerenstva)Granter University of Rijeka Defense date and country 2013-01-01, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 618 - Gynaecology. Obstetrics Abstract Cilj: Osnovni cilj ovog rada bio je utvrditi povezanost varijabilnosti gena matriks metaloproteinaza (MMP) i tkivnih inhibitora metaloproteinaza (TIMP) i etiologije idiopatskih ponavljajućih spontanih pobačaja (IPSP). Dodatno je istražena povezanost varijabilnosti navedenih gena i podložnosti za primarni i sekundarni IPSP.
Ispitanici: U istraživanje su bile uključene dvije skupine ispitanika, uključujući parove s IPSP-om i kontrolne ispitanike. Skupinu parova s IPSP-om činilo je 149 žena i
... More njihovih 149 reproduktivnih partnera sa tri ili više uzastopnih spontanih pobačaja nepoznate etiologije. Kontrolnu skupinu sačinjavalo je 149 zdravih žena i 149 zdravih muškaraca koji imaju barem dva živorođena djeteta, bez spontanih pobačaja i ostalih komplikacija u trudnoći.
Metode: Za genotipizaciju MMP-1 -1607 1G/2G, MMP-2 -735 C/T, MMP-2 -1306 C/T, MMP-3 -1612 5A/6A, MMP-9 -1562 C/T, te TIMP-1 -372 C/T, TIMP-2 -303 C/T, TIMP-3 -915 A/G, TIMP-3 -1296 C/T i TIMP-4 -3'-UTR C/T polimorfnih varijanti korištena je kombinacija metoda lančane reakcije polimerazom i polimorfizma duljine restrikcijskih fragmenata.
Rezultati: U žena s IPSP-om, u usporedbi s kontrolnom skupinom, pronađena je statistički značajno veća učestalost pojedinačnih MMP-2 -735 CT (P=0,006), MMP-2 -1306 CC (P=0,037) i MMP-9 -1562 CC (P=0,010) genotipova. Osim toga, izgledi za IPSP su dva puta veći u žena koje imaju MMP-2 -735 CT i TT u usporedbi s CC genotipom (OR=2,15; 95 % CI=1,34-3,45; P=0,001), MMP-2 -1306 CC u usporedbi s CT i TT genotipovima (OR=2,08; 95 % CI=1,17-3,69; P=0,012), kao i MMP-9 -1562 CC u usporedbi s CT i TT genotipovima (OR=2,21; 95 % CI=1,30-3,80; P=0,004). Međusobne kombinacije navedenih rizičnih genotipova, kao i njihove kombinacije s genotipovima drugih polimorfnih varijanti gena MMP i TIMP obitelji ne povećavaju izglede za IPSP u usporedbi s pojedinačnim rizičnim MMP-2 i -9 genotipovima. Raspodjele učestalosti genotipova, alela i haplotipova preostalih polimorfnih varijanti gena MMP i TIMP obitelji nisu se statistički značajno razlikovale između žena, kao niti muškaraca skupine parova s IPSP-om i kontrolne skupine.
U muških partnera žena sa sekundarnim IPSP-om, u usporedbi s primarnim IPSP-om, utvrđena je statistički značajno veća učestalost MMP-9 -1562 CC genotipa (P=0,015), koji povećava izglede za sekundarni IPSP 3,81 puta u usporedbi s CT i TT genotipovima (95 % CI=1,47-9,84; P=0,006). Kombinacije MMP-9 -1562 CC genotipa s genotipovima drugih polimorfnih varijanti gena MMP i TIMP obitelji ne povećavaju dodatno izglede za IPSP. Raspodjele učestalosti genotipova, alela i haplotipova preostalih polimorfnih varijanti gena MMP i TIMP obitelji nisu se statistički značajno razlikovale između žena, kao niti muškaraca podskupina primarnih i sekundarnih IPSP-ova.
Zaključak: Pojedinačni MMP-2 -735 CT, MMP-2 -1306 CC ili MMP-9 -1562 CC genotipovi mogući su čimbenici podložnosti za IPSP u žena. Također, MMP-9 -1562 CC genotip u muškaraca mogući je čimbenik podložnosti za sekundarni IPSP. Less Abstract (english) Objective: The main objective of this study was to determine the association of variation of matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) genes and the etiology of idiopathic recurrent spontaneous abortion (IRSA). Additionally, the association of variability in the afore-mentioned genes and susceptibility to primary and secondary IRSA was investigated.
Patients: Two groups of cases were included in this study, including the group of couples with IRSA
... More and control group. A total of 149 women and 149 of their reproductive partners with three or more consecutive spontaneous abortions of unknown etiology comprised the group of couples with IRSA. The control group included 149 healthy women and 149 healthy men with at least two live births and no history of pregnancy losses or any other pregnancy complications.
Methods: Genotyping of MMP-1 -1607 1G/2G, MMP-2 -735 C/T, MMP-2 -1306 C/T, MMP-3 -1612 5A/6A, MMP-9 -1562 C/T, as well as TIMP-1 -372 C/T, TIMP-2 -303 C/T, TIMP-3 -915 A/G, TIMP-3 -1296 C/T and TIMP-4 -3'-UTR C/T polymorphisms was performed using the combination of polymerase chain reaction and restriction fragment length polymorphism methods.
Results: Statistically significant higher frequency of individual MMP-2 -735 CT (P=0.006), MMP-2 -1306 CC (P=0.037) and MMP-9 -1562 CC (P=0.010) genotypes was found in women with IRSA compared with control women. Moreover, twofold increased odds of IRSA were determined in women with MMP-2 -735 CT and TT compared to CC genotype (OR=2.15; 95 % CI=1.34-3.45; P=0.001), MMP-2 -1306 CC compared to CT and TT genotypes (OR=2.08; 95 % CI=1.17-3.69; P=0.012), as well as MMP-9 -1562 CC compared to CT and TT genotypes (OR=2.21; 95 % CI=1.30-3.80; P=0.004). Combined analysis of these risk genotypes, as well as their combination with genotypes of other MMP and TIMP gene polymorphisms did not increase the odds of IRSA in comparison with individual MMP-2 and -9 risk genotypes. No statistically significant differences were determined in the distribution of genotypes, alleles and haplotypes frequencies of other MMP and TIMP gene polymorphisms between IRSA patients and controls.
A statistically significant higher frequency of MMP-9 -1562 CC genotype was found in male partners of women with secondary IRSA compared with primary IRSA (P=0.015). Men with MMP-9 -1562 CC genotype had 3,81 increased odds of secondary IRSA compared to men with CT and TT genotypes (95 % CI=1.47-9.84; P=0.006). The combinations of MMP-9 -1562 CC genotype with genotypes of other MMP and TIMP gene polymorphisms did not increase the odds of IRSA. No significant differences were found in the distribution of genotypes, alleles and haplotypes frequencies of other MMP and TIMP gene polymorphisms between the patients with primary and secondary IRSA.
Conclusion: Individual MMP-2 -735 CT, MMP-2 -1306 CC or MMP-9 -1562 CC genotypes could be factors of predisposition to IRSA in women. Additionally, MMP-9 -1562 CC genotype in men might be a factor of predisposition to secondary IRSA. Less Keywords
matriks metaloproteinaze
polimorfizam genetički
spontani pobačaj ponavljajući
tkivni inhibitor metaloproteinaza
trudnoća
Keywords (english)
matrix metalloproteinases
miscarriage recurrent
polymorphism genetic
pregnancy
tissue inhibitor of metalloproteinases.
Language croatian URN:NBN urn:nbn:hr:188:259290 Promotion 2020 Study programme Title: Biomedicine Postgraduate (doctoral) study programme Catalog URL https://libraries.uniri.hr/cgi-bin/unilib.cgi?form=D1130402078 Type of resource Text Extent 149 str; 30 cm File origin Born digital Access conditions Open access Terms of use Created on 2017-01-19 17:35:03
