3 research outputs found
Erratum to: A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland
The genetic spectrum of familial hypercholesterolemia in south-eastern Poland
BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder with a frequency of 1 in 200 to 500 in most European populations. Mutations in LDLR, APOB and PCSK9 genes are known to cause FH. In this study, we analyzed the genetic spectrum of the disease in the understudied Polish population. MATERIALS AND METHODS: 161 unrelated subjects with a clinical diagnosis of FH from the south-eastern region of Poland were recruited. High resolution melt and direct sequencing of PCR products were used to screen 18 exons of LDLR, a region of exon 26 in the APOB gene and exon 7 of PCSK9. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect gross deletions and insertions in LDLR. Genotypes of six LDL-C raising SNPs were used for a polygenic gene score calculation. RESULTS: We found 39 different pathogenic mutations in the LDLR gene with 10 of them being novel. 13 (8%) individuals carried the p.Arg3527Gln mutation in APOB, and overall the detection rate was 43.4%. Of the patients where no mutation could be found, 53 (84.1%) had a gene score in the top three quartiles of the healthy comparison group suggesting that they have a polygenic cause for their high cholesterol. CONCLUSIONS: These results confirm the genetic heterogeneity of FH in Poland, which should be considered when designing a diagnostic strategy in the country. As in the UK, in the majority of patients where no mutation can be found, there is likely to be a polygenic cause of their high cholesterol level
Intima-media thickness and selected parameters of endothelial function in patients with type 2 diabetes
WST臉P. Cukrzyca typu 2 stanowi powa偶ny problem
zdrowotny oraz ekonomiczny, co wi膮偶e si臋 przede
wszystkim z rozwojem jej przewlek艂ych powik艂a艅. Za
jeden z mechanizm贸w prowadz膮cych do ich powstawania
uwa偶a si臋 zaburzenia funkcji 艣r贸db艂onka.
Celem niniejszej pracy by艂a ocena wska藕nika grubo艣ci
kompleksu intima-media (IMT) i wybranych parametr贸w
funkcji 艣r贸db艂onka u chorych na cukrzyc臋
typu 2. Szczeg贸艂owe cele pracy obejmowa艂y:
- ocen臋 grubo艣ci IMT w t臋tnicach szyjnych wsp贸lnych
u chorych na cukrzyc臋 typu 2 oraz u os贸b
bez cukrzycy;
- ocen臋 wybranych parametr贸w funkcji wazomotorycznej
i wydzielniczej 艣r贸db艂onka naczyniowego
u chorych na cukrzyc臋 typu 2 oraz u os贸b bez
cukrzycy.
MATERIA艁 I METODY. Do badania w艂膮czono 182 chorych
na cukrzyc臋 typu 2, pozostaj膮cych pod opiek膮 poradni diabetologicznej przy Katedrze i Klinice Chor贸b
Metabolicznych w Krakowie. Cukrzyc臋 typu 2
rozpoznawano zgodnie z kryteriami WHO. Do badania
zakwalifikowano osoby z co najmniej 5-letnim
czasem trwania choroby, u kt贸rych cukrzyc臋 rozpoznano
po 35. roku 偶ycia i stosowano w nich leki doustne
przez co najmniej 2 lata po rozpoznaniu. Grup臋
kontroln膮 stanowi艂o 43 zdrowych, doros艂ych
ochotnik贸w, kt贸rzy wyrazili zgod臋 na udzia艂 w badaniu
i mieli prawid艂owe st臋偶enie glukozy na czczo
oraz prawid艂owy wynik doustnego testu tolerancji
glukozy. U wszystkich pacjent贸w przeprowadzono
podmiotowe i przedmiotowe badanie lekarskie oraz
pomiar IMT za pomoc膮 USG. Oceny funkcji 艣r贸db艂onka
dokonano poprzez pomiary:
- rozkurczu naczynia zwi膮zanego z reaktywnym
przekrwieniem t臋tnicy ramiennej metod膮 FMD;
- biochemicznych marker贸w funkcji 艣r贸db艂onka:
czynnika von Willebranda (vWf) i rozpuszczalnej
moleku艂y adhezyjnej (s-ICAM-1).
Analiza statystyczna obejmowa艂a metod臋 ANOVA,
test Manna-Whitneya, nieparametryczny test c2,
obliczenie wsp贸艂czynnika korelacji liniowej r-Pearsona.
Ponadto zastosowano wielokrotn膮 regresj臋
logistyczn膮.
WYNIKI. Przebadano 182 chorych na cukrzyc臋 typu 2,
w tym 91 kobiet (50,0%) i 91 m臋偶czyzn (50,0%) (艣redni
wiek w momencie badania - 56,3 roku) oraz 43 osoby
bez cukrzycy (艣redni wiek w momencie badania
- 55,4 roku) stanowi膮ce grup臋 kontroln膮. 艢rednie warto艣ci IMT by艂y istotnie wy偶sze, a maksymalne
warto艣ci FMD istotnie ni偶sze w grupie chorych na
cukrzyc臋 typu 2 ni偶 w grupie kontrolnej (odpowiednio:
0,83 mm vs. 0,66 mm; p < 0,00005 i 9,0% vs.
11,4%; p = 0,0165). Nie stwierdzono istotnych statystycznie
r贸偶nic pomi臋dzy st臋偶eniem s-ICAM-1
i czynnika von Willebranda w surowicy u chorych na
cukrzyc臋 typu 2 i u os贸b z grupy kontrolnej. W analizie
metod膮 regresji liniowej cukrzyca typu 2 okaza艂a
si臋 niezale偶nym predyktorem pogrubienia wska藕nika
IMT (p < 0,001). Cukrzyca typu 2 nie by艂a
w opisanym badaniu niezale偶nym czynnikiem ryzyka
w odniesieniu do pozosta艂ych badanych parametr贸w:
FMD oraz st臋偶e艅 vWF i s-ICAM-1.
WNIOSKI. Chorzy na cukrzyc臋 typu 2 cechuj膮 si臋 cz臋stym
wyst臋powaniem pogrubienia IMT oraz upo艣ledzeniem
funkcji rozkurczowej naczy艅 t臋tniczych.
Cukrzyca typu 2 jest niezale偶nym predyktorem pogrubienia
IMT.INTRODUCTION. Type 2 diabetes (DM 2) is a growing
health and economic problem, mainly because
of development of its chronic complications. One of
possible mechanisms leading to their occurrence is
endothelial dysfunction (ED).
The aim of the study was to asses intima-media thickness
(IMT) and selected parameters of ED in patients
with DM 2. Specific aims were:
- assessment of IMT in DM 2 and in the controls;
- assessment of selected parameters of vasomotor
and secretory function of endothelium in DM
2 patients and in the controls.
MATERIAL AND METHODS. We examined 182 patients
with DM 2 from the outpatient clinic of Department
of Metabolic Diseases, Jagiellonian University,
Medical College. Diabetes was diagnosed
according to WHO criteria. We included in our study
DM 2 patients with at least 5 years diabetes duration,
who were diagnosed after age 35 and were
treated with oral hypoglycemic agents for at least
2 years. The control group included 43 healthy volunteers
with normal fasting glucose level and correct
result of oral glucose tolerance test according to
WHO. All patients were examined and medical history
was taken. We also measured IMT by ultrasound.
We assessed endothelial function by
- flow-mediated dilatation (FMD) method;
- assessment of biochemical markers of ED - von
Willebrand factor (vWf) and s-ICAM-1 (soluble
intercellular adhesion molecule-1) concentrations.
Statistical analysis included ANOVA analysis, Mann-Whitney’s test, χ2 test, calculation of Pearson’s
linear correlation coefficient and multiple regression
analysis.
RESULTS. We examined 182 patients with type 2 DM
(mean age at the examination 56.3 yrs) including
91 (50%) women and 91 (50%) men together with
43 non-diabetic volunteers (mean age at the examination
55.4 years). Mean IMT was significantly higher
and maximal FMD lower in DM 2 patients than in
control group (respectively 0.83 mm vs. 0.66 mm;
p < 0.00005 and 9.0% vs. 11.4%; p = 0.0165). No
significant differences were found between groups
in respect to s-ICAM-1 and vWf concentration. In multiple
linear regression DM 2 was an independent predictor
of increased IMT (p < 0.001). DM 2 did not
appear to be a predictor of the other examined parameters:
FMD as well as vWF and s-ICAM-1 levels.
CONCLUSIONS. DM 2 patients are characterized by
the common occurence of increased IMT and endothelial
vasodilation function. DM 2 is an independent
predictor of intima-media thickening