The use of low density lipoprotein receptor activity of lymphocytes to determine the prevalence of familial hypercholesterolaemia in a rural South African community.

Abstract

SUMMARYThe diagnosis of heterozygous familial hypercholesterolaemia in three rural South African communities in which hypercholesterolaemia is very prevalent could be confirmed by the measurement of low density lipoprotein (LDL) receptor activity in circulating lymphocytes. A nominal cut off point could be proposed which separated the LDL receptor activity of 24 clinically diagnosed heterozygous FH patients and 31 healthy people. LDL receptor activity was measured as total degradation of 1251-LDL and expressed as ng LDLJmg cell protein/6 hours. The cut off point was set at 970 ng/mg protein/6 hours. This proposed cut off point was tested by assaying the LDL receptor of three homozygous FH patients and seven of their obligate heterozygous FH first degree relatives. The three homozygous FH patients showed no receptor activity and the activity of the seven obligate heterozygous first degree relatives fell below the proposed cut off point. To determine the prevalence of FH in the study population, all persons aged 15 to 24 years whose total cholesterol levels fell above the 80th centile for their age and sex, as well as their families, were approached (n= 114). The LDL receptor activity in lymphocytes of 77 of these persons aged 15 to 24 years was determined after applying the exclusion criteria. Ten of the 77 participants had LDL receptor activity below 970 ng LDIJmg protein/6 hours and were therefore diagnosed as being heterozygous FH patients. The calculation of the prevalence (corrected for exclusions) revealed that one in 71 of the 15 to 24 year old permanent residents in the predominantly Afrikaans speaking community suffered from heterozygous FH. This is higher than any FH prevalence previously reported for any group.

Recent Origin and Spread of a Common Lithuanian Mutation, G197del LDLR, Causing Familial Hypercholesterolemia: Positive Selection Is Not Always Necessary to Account for Disease Incidence among Ashkenazi Jews

“…More than 680 LDLR mutations have been identified (Varret et al 1998 [LDLR Database]; Heath et al 2001 [The Low Density Lipoprotein Receptor (LDLR) Gene in Familial Hypercholesterolemia]). In relatively isolated populations-including the French Canadians in northeastern Quebec (Moorjani et al 1989;Leitersdorf et al 1990), Afrikaners in South Africa (Steyn et al 1989;Kotze et al 1991), Ashkenazi Jew (AJ) individuals (Seftel et al 1989;Meiner et al 1991), Druze (Landsberger et al 1992), Christian Lebanese (Lehrman et al 1987), Finns (Aalto-Setala et al 1992Koivisto et al 1992), and Tunisians (Slimane et al 1993)-there is an increased prevalence of FH, which reaches its height in AJ individuals (in whom the frequency is 1 heterozygote per 67-69 individual [Seftel et al 1989]). In these populations, a small number of LDLR mutations predominate, which either were introduced at a founder time or appeared in more-recent generations.…”

Long-term follow-up in patients with homozygous familial hypercholesterolemia; 13-year experience of a university hospital lipid clinic

“…[8][9][10][11][12][13] En yüksek AH prevelansının Güney Afrika'da (HeAH sıklığı 70'te 1) olduğu bildirilmiştir. [11] Fransız Kanadalılarda ise 270'te 1 kişinin HeAH olduğu tahmin edilmektedir. [12] Lübnan'da HoAH prevalansı 10.000'de 1 gibi daha yüksek orandadır.…”

LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives

“…In most investigated populations, the heterozygote form occurs in at least 1:500 and the homozygous form in one in one million individuals [ 15 ], although in some populations, for example the Afrikaner population in South Africa, heterozygosity is found in less than 1:80 individuals [ 16 , 17 ]. This unusual high frequency is due to founder effects and no heterozygote advantage has been identified.…”