Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2013, vol. 22, nr 1, January-February, p. 57–67

Publication type: original article

Language: English

Phenotype-Genotype Analyses of Clinically Diagnosed Malaysian Familial Hypercholestrolemic Patients

Analiza zależności genotyp-fenotyp u Malezyjczyków chorych na rozpoznaną klinicznie rodzinną hipercholesterolemię

Alyaa Al-Khateeb1,B,C,D,E, Hassanain Al-Talib1,D,E,F, Mohd S. Mohamed2,A,E,F, Zurkurnai Yusof3,A, Bin A. Zilfalil4,A,B,C,D,E,F

1 Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia

2 Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia

3 Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

4 Department of Pediatric, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

Abstract

Background. Familial hypercholesterolemia and familial defective apo lipoprotein B are genetic disorders caused by defects in the low-density lipoprotein receptor gene and apo lipoprotein B 100 genes, respectively. The clinical phenotype of both diseases is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature coronary heart disease.
Objectives. The aim of this study is to perform an association study between different gene sequence variants in low-density lipoprotein and apo lipoprotein B 100 genes to the clinical finding and lipid profile parameters of the study subjects.
Material and Methods. A group of 164 familial hypercholesterolemic patients were recruited. The promoter region, exon 2–15 of the low density lipoprotein gene and parts of exon 26 and 29 of apo lipoprotein B 100 gene were screened by Denaturating Gradient High Performance Liquid Chromatography.
Results. For the apo lipoprotein B 100 gene, those with apo lipoprotein B 100 gene mutation have a significantly higher frequency of cardiovascular disease (P = 0.045), higher low density lipoprotein cholesterol and total cholesterol: high density lipoprotein cholesterol ratio than those without mutation (P = 0.03 and 0.02, respectively). For the low density lipoprotein gene defect those with frame shift mutation group showed the worst clinical presentation in terms of low density lipoprotein cholesterol level and cardiovascular frequency.
Conclusion. There was a statistically significant association between mutations of low density lipoprotein gene and apo lipoprotein B 100 genes and history of cardiovascular disease, younger age of presentation, family history of hyperlipidemia, tendon xanthoma and low density lipoprotein cholesterol level.

Streszczenie

Wprowadzenie.Rodzinna hipercholesterolemia i rodzinnie uszkodzona lipoproteina apo B są to genetyczne zaburzenia spowodowane przez uszkodzenie odpowiednio genu receptora lipoprotein małej gęstości i genów apo B 100. Kliniczny fenotyp obu chorób charakteryzuje się zwiększeniem stężenia cholesterolu całkowitego i cholesterolu lipoprotein małej gęstości, żółtakami ścięgna i przedwczesną chorobą wieńcowej.
Cel pracy. Ocena związków między różnymi wariantami sekwencji genów lipoprotein o małej gęstości i genów apo B 100 a rozpoznaniem klinicznym i parametrami profilu lipidowego badanych chorych.
Materiał i metody. Do badań włączono grupę 164 pacjentów chorych na hipercholesterolemię rodzinną. Region promotora, ekson 15/2 lipoprotein o małej gęstości i części eksonu 26 i 29 genu apo B 100 przeszukiwano metodą wysokosprawnej chromatografii cieczowej z czynnikiem denaturującym.
Wyniki. Dla genów apo lipoproteiny B 100, w pacjentów z mutacją genu apo lipoproteiny B 100 choroby sercowo-naczyniowe występują częściej (p = 0,045), stężenie cholesterolu lipoprotein małej gęstości jest większe i stosunek całkowitego cholesterolu do cholesterolu lipoprotein dużej gęstości niż u pacjentów bez mutacji (P = 0,03 i 0,02 odpowiednio). W przypadku wady genetycznej lipoprotein małej gęstości u pacjentów z mutacją zmiany fazy odczytu ich stan kliniczny był najgorszy pod względem stężenia cholesterolu lipoprotein o małej gęstości i częstotliwości występowania chorób krążenia.
Wnioski. Stwierdzono statystycznie istotny związek między mutacjami genu lipoprotein małej gęstości i genów lipoprotein apo B 100 oraz chorobami układu krążenia w wywiadzie, młodszym wiekiem wystąpienia chorób, rodzinną hiperlipidemią w wywiadzie, żółtakami ścięgna i stężeniem cholesterolu lipoprotein małej gęstości.

Key words

phenotypic characters, LDLR, APOB-100, familial hypercholesterolemia, premature coronary heart disease, polymorphism.

Słowa kluczowe

cechy fenotypowe, LDLR, APOB-100, rodzinna hipercholesterolemia, przedwczesna choroba niedokrwienna serca, polimorfizm.

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