OBJECTIVES: The newborn screening (NBS) program in the Republic of Serbia has several decades of tradition, but it has not included any organic acidemias (OA). Therefore, this study aimed to establish the cut-offs of the corresponding NBS markers in the population of healthy newborns. METHODS: In dried blood samples (DBS) collected from 1,771 healthy newborns, we analyzed levels of propionylcarnitine (C3), isovalerylcarnitine (C5), and glutarylcarnitine (C5DC) using tandem mass spectrometry. Further we calculated the following ratios: C3/acetylcarnitine (C3/C2), C3/palmitoylcarnitine (C3/C16), C5/ free carnitine (C0), C5/C2, C5/C3, C5DC/octanoylcarnitine (C8), and C5DC/C0. RESULTS: The cut-offs for methylmalonic acidemia (MMA) or propionic acidemia (PA) were C3>5.73 μmol/L, C3/C2>0.23, and C3/C16>2.36. Based on the study findings, the screening results indicative for isovaleric acidemia (IVA) would include C5>0.372 μmol/L, C5/C0>0.020, C5/C2>0.019, and C5/C3>0.31. Finally, C5DC>0.303 μmol/L, C5DC/C8>7.1, and C5DC/C0>0.019 would justify further testing for glutaric acidemia type I (GA1). The cut-offs were satisfactorily validated via the comparison with worldwide estimates and data for several Caucasian populations. CONCLUSIONS: The levels of the OA biomarkers in the Serbian population of healthy newborns have a distribution pattern similar to the other world populations. Therefore, the proposed cut-offs represent a reliable starting point for the future development of the OA NBS.
- MeSH
- biologické markery MeSH
- glutaryl-CoA-dehydrogenasa nedostatek MeSH
- isovaleryl-CoA-dehydrogenasa MeSH
- lidé MeSH
- metabolické nemoci mozku MeSH
- novorozenec MeSH
- propionová acidemie * diagnóza MeSH
- vrozené poruchy metabolismu aminokyselin MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Srbsko MeSH
Objectives Cytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin. Methods Roma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay. Results We found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics. Conclusions There were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.
- MeSH
- cytochrom P-450 CYP1A2 genetika metabolismus MeSH
- cytochrom P-450 CYP2D6 genetika metabolismus MeSH
- cytochrom P450 CYP2A6 genetika metabolismus MeSH
- cytochrom P450 CYP2B6 genetika metabolismus MeSH
- dospělí MeSH
- genotyp MeSH
- lidé MeSH
- polymorfismus genetický genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS: Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci. RESULTS: Distribution of rs6535454 in patients with SAMS (GG=51.1%, GA=40.0%, AA=8.9%) did not significantly differ (p=0.33; respectively 0.32 for codominant models of the analysis) from that in the population controls (GG=48.1%, GA=45.0%, AA=6.9%) or the SAMS-unaffected patients (GG=49.8%, GA=40.3%, AA=9.7%). Similarly, neither rs4693075 was associated with SAMS (CC=36.8%, CG=48.2%, GG=15.0% in patients suffering SAMS vs. CC=36.6%, CG=47.5%, GG=15.9 in controls and CC=35.8%, CG=48.2%, GG=15.9% in symptom-free patients, p=0.94 and 0.95 for codominant models of the analysis). Also, the haplotype distributions were not significantly different between the groups analyzed. CONCLUSIONS: The polymorphisms of the COQ2 gene do not associate with SAMS in the Czech patients treated with low doses of statins. This is another clue that the coenzyme Q10 pathway is not the most important for the development of SAMS.
- MeSH
- běloši genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- haplotypy MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci svalů chemicky indukované epidemiologie genetika MeSH
- polymorfismus genetický genetika MeSH
- statiny škodlivé účinky MeSH
- studie případů a kontrol MeSH
- ubichinon genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
