Heteromorphisms of human chromosomes in reproductive disorders

Cilj: U radu je istražena učestalost varijanata konstitutivnog heterokromatina (KH) u osoba s različitim poremećajima reprodukcije (primarni ili sekundarni sterilitet, jedan ili više spontanih pobačaja), te kliničkim dijagnozama kriptorhizma ili hipogonadizma, gojaznosti ili ginekomastije. Metode: Prisutnost kromosomskih heteromorfizama procijenjena je u 499 osoba tijekom rutinske kariotipizacije izvedene na GTG-opruganim metafaznim kromosomima dobivenim iz fitohemaglutininom stimuliranih limfocita periferne krvi. Rezultati: Varijante KH-a u pronađene su u 22,6 % ispitanika. Najviša je učestalost nositelja zabilježena u skupini s primarnim sterilitetom (28,7 %) i značajno je viša negoli u skupini s dva ili više spontanih pobačaja (15,4 %) (OR = 2,209; CI = 1,175 – 4,153; P = 0,014). Od pojedinačnih varijanata najčešće su zabilježene varijacije D-grupe kromosoma (9,6 %), a slijede varijante 9qh, Yqh, 16qh, varijante G-grupe i 1qh (5,1 %, 4,9 %, 4,0 %, 2,7 % i 2,0 %). Varijanta heterokromatina inv(9) pojavljuje se učestalošću od 1,6 %. Budući da su pojedini ispitanici (6,5 %) nositelji multiplih varijanata, ukupan broj varijanata u pojedinim dijagnostičkim skupinama varira između 20,2 % i 39,6 %. Ponovno, najviša je učestalost u skupini s primarnim sterilitetom (39,6 %), dok je najniža u skupini s dva i više spontanih pobačaja (20,2 %) (OR = 2,595; CI = 1,465 – 4,598; P = 0,001). Zaključak: Značajno viša učestalost kromosomskih heteromorfizama u osoba s primarnim sterilitetom podupire hipotezu prema kojoj kromosomski heteromorfizmi nisu bezazlene varijante, već bi mogli, mehanizmima koje ne razumijemo u potpunosti, umanjivati reproduktivnu sposobnost čovjeka.Aim: The frequency of heterochromatin variants was determined in the group of patients with defective reproductive fitness (primary or secondary sterility, history of one or more spontaneous abortions), in those with clinical diagnoses of cryptorchidism or hypogonadism, and obesity or gynecomastia. Methods: The chromosomal heteromorphisms were evaluated in 447 individuals during routine karyotipization on GTG-banded metaphase slides prepared from phytohemaglutinin-stimulated peripheral blood lymphocytes. Results: The overall frequency of heterochromatin variants was 22.6 %. The highest frequency of variants was determined in the primary sterility group (28.7 %). The difference was statistically significant in comparison with the two or more – spontaneous abortion group (15.4 %) (OR=2,209; CI=1,175-4,153; P=0,014). The most frequent were D-group chromosomal variants (9,6 %) followed by 9qh, Yqh, 16qh, Ggroup variants and 1qh ((5,1 %, 4,9 %, 4,0 %, 2,7 % and 2,0 %, respectively). The variant inv(9) was represented with 1.6 %. Because 6,5 % of subjects in the study carried multiple variants in their karyotype, the total number of variants between diagnoses varied between 20,2 % and 39,6 %. The highest frequency of variants was observed in the primary sterility group (39,6 %). It was significantly different when compared to the two or more – spontaneous abortion group (20,2 %) (OR=2,595; CI=1,465-4,598; P=0,001). Conclusion: Significantly higher frequency of chromosomal heteromorphisms in individuals with primary sterility supports the view of chromosomal variants being not harmless variants. By mechanism(s) not fully understood yet, chromosomal heteromorphisms might decrease the reproductive fitness in humans