» arhiv
Možnosti:
[Prikaži v obliki za tiskanje]
[Naloga še ni vpisana v zbirko Cobiss]
ID naloge: 152 Letnik: 2003 Predmet: interna medicina
PRIMARNA BILIARNA CIROZA IN OSTEOPOROZA: VPLIV POLIMORFIZMOV GENA ZA OSTEOPROTEGERIN
Avtor: Aleš Skvarca, Matej Godnic
Mentor: prof. dr. Janez Preželj
Somentor: asist. dr. Tomaž Kocjan
IZHODIŠCE: Vecina opravljenih raziskav kaže, da je osteoporoza pogost zaplet pri bolnicah s primarno biliarno cirozo (PBC). Osteoporoza je zmanjšanje mineralne kostne gostote (MKG) za vec kot 2,5 standardne deviacije od najvecje MKG v odrasli dobi. Nedavno so odkrili skupino treh proteinov, ki sodelujejo v diferenciaciji in aktivaciji v kostni razgradnji sodelujocih osteoklastov. To so aktivator receptorja jedrnega faktorja ?B (RANK), RANK ligand (RANKL) in osteoprotegerin (OPG). OPG s prestrezanjem RANKL preprecuje njegovo vezavo na RANK in s tem zavira osteoklastogenezo. Pri bolnikih z osteoporozo so ugotovili povezavo med polimorfizmom gena za OPG in stopnjo osteoporoze.
NAMEN: Genetske faktorje kot možne napovedovalce ogroženosti bolnic s PBC zaradi osteoporoze so priceli raziskovati šele nedavno. Namen naše študije je bil ugotoviti vpliv polimorfizmov gena za OPG na MKG pri bolnicah s PBC. Podatki o tem v literaturi še niso bili objavljeni.
HIPOTEZA: Želeli smo preveriti naslednjo hipotezo: pojavljanje osteoporoze pri bolnicah s primarno biliarno cirozo je v povezavi s polimorfizmi gena za osteoprotegerin.
METODE: V presecno študijo je bilo vkljucenih 27 bolnic s PBC, ki se kontrolirajo v ambulanti Klinicnega oddelka za gastroenterologijo v Klinicnem centru v Ljubljani. Vse bolnice so jemale ursodeoksiholno kislino. Razen preparatov kalcija in vitamina D nobena bolnica ni jemala zdravil, ki bi lahko pomembno vplivala na mineralno kostno gostoto ali na kazalce kostne premene. Vsem bolnicam smo opravili biokemicne preiskave krvi in klinicni pregled. Izmerili smo jim mineralno kostno gostoto ledvene hrbtenice (L1 do L4) in levega kolka z dvoenergijsko rentgensko absorpciometrijo. Za dolocevanje polimorfizmov gena za OPG in gena za receptor vitamina D smo iz levkocitov periferne krvi izolirali DNK. Fragmente smo pomnožili z reakcijo verižnega pomnoževanja. Genotipe smo dolocili z metodo analize dolžin restrikcijskih fragmentov. Rezultate smo statisticno obdelali s 2 - testom, Studentovim t-testom, analizo variance in Mann-Whitneyevim testom. P vrednosti pod 0,05 smo upoštevali kot statisticno pomembne.
REZULTATI: Pri nobeni izmed sedmih (7) bolnic s PCB in z genotipom AG nismo ugotovili osteoporoze. Od bolnic z genotipom AA pa jih je 10 razvilo osteoporozo, drugih 10 pa ne. Povezava med polimorfizmom 163 A G gena za OPG in pojavom osteoporoze je statisticno znacilna (p=0,021). Bolnice z genotipom AG so imele v primerjavi z bolnicami z genotipom AA absolutno vecjo MKG na vseh mestih merjenja. Razlika v ledvenem predelu je bila na meji statisticne pomembnosti (p=0,061). Skupina bolnic s PBC z osteoporozo in skupina bolnic s PBC brez osteoporoze se nista pomembno razlikovali v spremenljivkah, ki so povezane z MKG (starost, indeks telesne mase, leta po menopavzi, itd.). Povezave med MKG in tistimi spremenljivkami, ki so povezane s PBC (koncentracija bilirubina, aktivnost jetrnih transaminaz, trajanje bolezni), nismo našli. Skupini bolnic z genotipom AA oz. AG se statisticno pomembno (p=0,04) razlikujeta v razmerju precno povezanih C-terminalnih telopeptidov kolagena I in osteokalcina (CTX-I/OC), ki smo ga uporabili kot oznacevalca povezave med razgradnjo in izgradnjo kosti.
ZAKLJUCKI: Z našo raziskavo smo potrdili povezavo med pojavljanjem osteoporoze pri bolnicah s primarno biliarno cirozo in polimorfizmom 163 A G gena za osteoprotegerin. Genotip AG je statisticno znacilno povezan z vecjo mineralno kostno gostoto. Skupini bolnic z genotipom AA oz. AG se statisticno pomembno razlikujeta v razmerju med razgradnjo in izgradnjo kosti.
«»
[Abstract / English version]
PRIMARNA BILIARNA CIROZA IN OSTEOPOROZA: VPLIV POLIMORFIZMOV GENA ZA OSTEOPROTEGERIN
Author: Aleš Skvarca, Matej Godnic
Mentor: prof. dr. Janez Preželj
Co-mentor: asist. dr. Tomaž Kocjan
BACKGROUND: Osteoporosis is a common complication of primary biliary cirrhosis (PBC). Osteoporosis is defined as a reduction of bone mineral density (BMD) value more than 2.5 standard deviations below the young adult mean value. Recently, three proteins that regulate differentiation and activation of osteoclasts were discovered. These are receptor activator of nuclear factor B (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). OPG acts as a decoy receptor for RANKL and thereby, by preventing its linkage to RANK, inhibits osteoclastogenesis. A correlation between OPG gene polymorphisms and osteoporosis has also been found.
AIM: Genetic factors as possible predictors of bone loss in patients with PBC were explored only recently. The aim of our research was to determine the influence of OPG gene polymorphisms on BMD in patients with PBC. No such data has been published yet.
HYPOTHESIS: Our hypothesis was: occurrence of osteoporosis in patients with PBC is associated with OPG gene polymorphisms.
METHODS: In our study twenty-seven (27) patients with PBC were evaluated. All of them were treated with ursodeoxycholic acid, but none of them had previously taken any drugs known to influence bone metabolism, except calcium and vitamin D. Clinical examination and biochemical tests were performed. BMD was measured with dual energy X-ray absorptiometry (DEXA) in lumbal area and left hip. For OPG gene polymorphisms analysis deoxyribonucleic acid (DNA) was isolated from peripheral blood leukocytes. For OPG gene polymorphisms analysis fragments of DNA were multiplied with polymerase chain reaction (PCR). Afterwards, genotypes were determined with restriction fragment length polymorphism (RFLP). CTX-I/OC (cross-linked C-terminal telopeptides of collagen type I/osteocalcin) ratio was calculated in all patients to define their bone turnover. Results were statistically analysed with 2 -test, Student t-test, ANOVA and Mann-Whitney test. P value below 0.05 was considered statistically significant.
RESULTS: None of seven (7) patients with PBC and AG genotype developed osteoporosis. Ten (10) of the patients with AA genotype developed osteoporosis and the other ten (10) did not. The correlation between 163 A G OPG gene polymorphism and occurrence of osteoporosis was statistically significant (p=0.021). Furthermore, patients with AG genotype had higher BMD than patients with AA genotype. This correlation was marginally statistically significant (p=0.061). Group of patients with PBC and osteoporosis and group of patients with PBC without osteoporosis did not significantly differ in variables usually correlated with BMD (age, body mass index (BMI), years after menopause, etc.). There was no correlation between BMD and variables connected with PBC (serum bilirubin, transaminases, duration of PBC). Patients with AA genotype had significantly higher CTX-I/OC ratio when compared to patients with AG genotype (p=0.040).
CONCLUSIONS: Our study confirmed the correlation between occurrence of osteoporosis in patients with PBC and 163 A G OPG gene polymorphism. Patients with AG genotype had significantly higher BMD. There was also a significant difference in bone turnover ratio between patients with AG genotype and patients with AA genotype.
|
|
 |
Išči po nalogah
Brskaj po nalogah
|
