| Abstract | Prirođene srčane greške javljaju se u oko 40 % do 60 % osoba sa sindromom Down. Enzim 5- metiltetrahidrofolat-homocistein metiltransferaza reduktaza (MTRR) ima ključnu ulogu u regulaciji metabolizma L-homocisteina. Istraživanja ukazuju da jednonukleotidni polimorfizmi gena kao i okolišni čimbenici mogu utjecati na razvoj prirođenih srčanih grešaka u osoba sa
sindromom Down.
Cilj: Utvrditi je li jednonukleotidni polimorfizam 66A > G MTRR povezan s nastankom prirođenih srčanih grešaka u osoba sa sindromom Down. Dodatno, ispitati utjecaj endogenih čimbenika majki djece sa sindromom Down na razvoj prirođenih srčanih grešaka kao što su dob, stanje uhranjenosti i unos folata putem prehrane te perikoncepcijski unos pripravaka folne kiseline, pušenje cigareta i uživanje alkohola.
Ispitanici i postupci: U istraživanje je uključeno 155 osoba sa sindromom Down i 148 njihovih majki. Kontrolna skupina je sačinjena od osoba sa sindroma Down bez prirođenih srčanih grešaka. Genotipizacija jednonukleotidnog polimorfizma 66A > G MTRR izvedena je PCRRFLP postupkom.
Rezultati istraživanja: Raspodjela i učestalost genotipova i alela jednonukleotidnog polimorfizma 66A > G MTRR nije statistički značajno različita u osoba sa sindromom Down kao ni njihovih majki, odnosno između skupine s prirođenim srčanim greškama u odnosu na skupinu bez prirođenih srčanih grešaka. Majke djece sa sindromom Down koje su pušile prije trudnoće i u vrijeme prikupljanja podataka imaju češće dijete sa sindromom Down kod kojeg je prisutna klijetno-koronarna cijev (p = <0,001), nego one koje nisu nikada pušile (p = 0,024). Majke djece sa sindromom Down čiji je oblik prehrane tijekom trudnoće bila sredozemna
prehrana statistički značajno češće imaju dijete sa sindromom Down kod kojeg je prisutna nepravilnost endokardijalnih jastučića, nego one čiji je oblik prehrane bio drugačiji (p = 0,043). Majke djece sa sindromom Down koje su tijekom trudnoće imale sredozemni oblik prehrane imaju otprilike šesterostruko veće izglede imati dijete s nepravilnošću endokardijalnih jastučića od onih čiji je oblike prehrane tijekom trudnoće bio drugačiji (OR = 0,163, 95 % CI [0,028 - 0,939]). Majke djece sa sindromom Down koje su uzimale pripravke folne kiseline od četvrtog tjedna prije trudnoće pa do osmog tjedna trudnoće češće imaju dijete sa sindromom Down koje ima prirođenu srčanu grešku (p = 0,013). Isto tako majke djece sa sindromom Down koje su uzimale pripravke folne kiseline od četvrtog tjedna prije trudnoće do osmog tjedna trudnoće češće imaju dijete s pregradnom greškom pretklijetke (p = 0,004).
Mlađe majke djece sa sindromom Down češće imaju dijete sa sindromom Down koje ima nepravilnost endokardijalnih jastučića (p = 0,010). Majke djece sa sindromom Down koje su uzimale pripravke folne kiseline tijekom trudnoće imaju skoro dvostruko veće izglede da će im dijete sa sindromom Down imati prirođenu srčanu grešku od majki djece sa sindromom Down koje nisu uzimale pripravke folne kiseline tijekom trudnoće (OR = 1,822, 95% CI [1,063 - 3,333]). Isto tako majke djece sa sindromom Down kod kojih je prisutan alel G jednonukleotidnog polimorfizma MTRR 66A > G imaju otprilike deveterostruko manje izglede da će im dijete sa sindromom Down imati prirođenu srčanu grešku ako je njihov oblik prehrane tijekom trudnoće kontinentalna prehrana (OR = 0,109, 95% CI 95% [0,014 – 0,872]). Isto tako majke djece sa sindromom Down koje su mutiranog homozigotnog genotipa jednonukleotidnog polimorfizma MTRR 66A > G, a koje su uzimale pripravke folne kiseline od četvrtog tjedna prije trudnoće do osmog tjedna trudnoće češće imaju djecu s pregradnom greškom klijetke (p = 0,036).
Zaključak: Rezultati istraživanja ukazuju kako polimorfizam MTRR 66A > G majki udružen s njihovim životnim navikama kao što su pušenje cigareta, oblik prehrane i uzimanje pripravaka folne kiseline može predstavljati rizik za nastanak prirođenih srčanih grešaka u djece sa sindrom Down. |
| Abstract (english) | Congenital heart defects are present in 40% to 60% of people with Down syndrome. The 5- methyltetrahydrofolate-homocysteine methyltransferase reductase enzyme (MTRR) is crucial for the regulation of L-homocysteine metabolism. Research shows that single-nucleotide polymorphisms and the environment can affect the development of congenital heart defects in people with Down syndrome.
Aim: To determine whether MTRR 66A>G single-nucleotide polymorphism is linked with the occurrence of congenital heart defects in people with Down syndrome. In addition, the aim is to examine the impact of endogenic factors, such as age, nutritional status, and dietary folate intake, as well as periconceptional folic acid intake, smoking, and alcohol consumption, in mothers with Down syndrome children on the development of congenital heart defects.
Subjects and Methods: The study includes 155 people with Down syndrome and 148 of their mothers. The control group consists of people with Down syndrome without congenital heart defects. The genotyping of MTRR 66A>G single-nucleotide polymorphism is by the PCRRFLP procedure.
Results: The distribution and frequency of genotypes and alleles of MTRR 66A>G singlenucleotide polymorphism are not statistically significantly different in people with Down syndrome and their mothers, i.e. between the group with congenital heart defects and the group without congenital heart defects. Mothers of Down syndrome children who smoked prior to
pregnancy and during the data collection are more likely to have a Down syndrome child with ventriculo-coronary arterial connection (p = < 0.001) than mothers who have never smoked (p = 0.024). Mothers of Down syndrome children who ate a Mediterranean diet during pregnancy were statistically more likely to have Down syndrome children with endocardial cushion defect than those who ate a different diet (p = 0.043). Mothers of Down syndrome children who ate a
Mediterranean diet during pregnancy had an approximately sixfold increase in the chances of having a child with endocardial cushion defect than those who ate a different diet during pregnancy (OR = 0.163, 95% CI [0.028 – 0.939]. Mothers of Down syndrome children who took periconceptional folic acid supplementation from week four before pregnancy until week eight of pregnancy were more likely to have a Down syndrome child with a congenital heart defect (p = 0.013). Likewise, mothers of Down syndrome children who took periconceptional folic acid supplementation from week four before pregnancy until week eight of pregnancy were more likely to have a Down syndrome child with a atrial septal defect (p = 0.004).
Younger mothers of Down syndrome children were more likely to have a Down syndrome child with endocardial cushion defect (p = 0.010). Mothers of Down syndrome children who took periconceptional folic acid supplementation during pregnancy were almost two times more likely to have a Down syndrome child with a congenital heart defect than mothers of Down syndrome children who did not take periconceptional folic acid supplementation during pregnancy (OR = 1.822, 95% CI [1.063 - 3.333]). Likewise, mothers of Down syndrome children with the G allele of MTRR 66A>G single-nucleotide polymorphism had about a ninefold decrease in the chances of having a Down syndrome child with a congenital heart
defect if they ate a continental diet during pregnancy (OR = 0.109, 95% CI 95% [0.014 – 0.872]). Moreover, mothers of Down syndrome children with a homozygous genotype mutation of MTRR 66A>G single-nucleotide polymorphism who took periconceptional folic acid supplementation from week four before pregnancy until week eight of pregnancy were more likely to have children with a ventricular septal defect (p = 0.036).
Conclusion: The study results show that the mother’s MTRR 66A>G single-nucleotide polymorphism in combination with lifestyle habits such as smoking, diet type, and periconceptional folic acid supplementation may pose a risk for the development of congenital heart defects in children with Down syndrome. |
