Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.


Keywords: apolipoprotein B; hypercholesterolaemia; low density lipoprotein receptor; mutation     

Hyperhomocysteinemia and the response to vitamin supplementation

Summary The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 mol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 mol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomo-cysteinemia.Abbreviations HPLC high-performance liquid chromatography - Lp(a) lipoprotein(a) - PLP pyridoxal 5-phosphate     

Biochemical responses during recovery from maximal and submaximal swimming exercise

Summary We set out to demonstrate whether changes in plasma volume, haematocrit and some important blood constituents occurred after swimming 100 m and 800 m, as well as monitoring the duration of these changes. We measured exercise-induced changes in concentration of plasma constituents in eight subjects, and determined the expected effects of haemoconcentration on these constituents. We also investigated the different biochemical responses occurring after maximal exercise (100 m), as compared to submaximal exercise (800 m). The haematocrit increased significantly after the 100 m swim and to a lesser extent after the 800-m swim, returning to basal levels within 30 min. The plasma volume decreased by 16% on completion of the 100 m and by 8% on completion of the 800 m. The blood lactate concentration increased 15-fold and 10-fold after the 100-m and 800-m swims respectively. The plasma potassium concentration increased significantly immediately on completion of the 100-m swim, then decreased significantly at 2 1/2 and 5 min post-exercise, returning to near-basal values at 30 min. The potassium concentration measured after the 800-m event did not differ significantly from basal levels, however the measured concentrations were significantly lower than the concentrations expected on the basis of haemoconcentration. The plasma sodium concentrations measured after both 100-m and 800-m swims were significantly increased. However, calculations correcting for haemoconcentration showed significant losses in toal circulating sodium. Our study demonstrates marked changes in plasma volume and certain blood constituents after maximal intensity swimming, and less marked changes after submaximal exercise. We also demonstrated the importance of taking the effects of haemoconcentration into account when evaluating changes in concentration of plasma constituents.     

Ethnic immunity to coronary heart disease?

Dietary fat intake is often regarded as a major determinant of coronary heart disease (CHD) rate and it has been deemed unnecessary to invoke racial or other factors to explain the differences in CHD rates among different ethnic groups. Despite a high prevalence of CHD risk factors such as hypertension, obesity, and smoking, CHD remains a rarity in westernized black Africans. Cord blood total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and apolipoprotein B (apo B) levels were measured and found to be respectively 12.1%, 18.3% and 22.4% lower in black neonates when compared to white neonates. These differences were again studied in a group of young black African males and a comparable group of age-matched whites who had been exposed to the same environment and western diet for at least 2 years. Although the body mass indices and serum albumin concentrations in the adult males were not significantly different, serum levels of TC, LDLC and apo B were 10.7%, 18.7% and 39.7% lower in the blacks, respectively. Furthermore, high density lipoprotein cholesterol (HDLC) and Apolipoprotein AI were 20.2% and 9.5% higher, homocysteine 45.6% lower and coagulation factor VII 26.6% lower in the adult black Africans. It is concluded that blacks are biochemically less responsive to an atherogenic diet than whites and these differences are already present at birth.     

A community-based study to examine the effect of a youth HIV prevention intervention on young people aged 15-24 in South Africa: results of the baseline survey

OBJECTIVES: To determine whether South African youths living in communities that had either of two youth human immunodeficiency virus (HIV) prevention interventions [(a) loveLife Youth Centre or (b) loveLife National Adolescent Friendly Clinic Initiative] would have a lower prevalence of HIV, sexually transmitted infections (STIs), and high risk sexual behaviours than communities without either of these interventions. METHODS: In 2002 the baseline survey of a quasi-experimental, community-based study was conducted in South Africa. In total 33 communities were included in three study arms (11 communities per study arm). The final sample included 8735 youths aged 15-24 years. All participants took part in a behavioural interview and were tested for HIV, gonorrhoea (Neisseria gonorrhoeae) and Chlamydia (Chlamydia trachomatis). RESULTS: HIV prevalence was 20.0% among females and 7.5% among males (OR 3.93 95% CI 2.51-6.15). There were no significant differences between study arms for HIV, NG or CT prevalence at baseline. In multiple regression analyses, HIV was significantly associated with NG infection (OR 1.96 95% CI 1.24-3.12) but not with CT infection. Youths who reported >1 lifetime partner were also significantly more likely to be infected with HIV (OR 1.98 95% CI 1.55-2.52), as were those who reported ever having engaged in transactional sex (OR 1.86 P = 0.02) or having had genital ulcers in the past 12 months (OR 1.71 P < or = 0.001). CONCLUSIONS: HIV prevention programmes must ensure that gender inequities that place young women at greater risk for HIV infection are urgently addressed and they must continue to emphasize the importance of reducing the number of sexual partners and STI treatment.     

Young people's sexual health in South Africa: HIV prevalence and sexual behaviors from a nationally representative household survey

OBJECTIVES: To determine the prevalence of HIV infection, HIV risk factors, and exposure to national HIV prevention programs, and to identify factors associated with HIV infection among South African youth, aged 15-24 years. DESIGN: A cross-sectional, nationally representative, household survey. METHODS: From March to August 2003 we conducted a national survey of HIV prevalence and sexual behavior among 11 904 15-24 year olds. Multivariable models for HIV infection were restricted to sexually experienced youth. RESULTS: Young women were significantly more likely to be infected with HIV in comparison with young men (15.5 versus 4.8%). Among men, a history of genital ulcers in the past 12 months was associated with HIV infection [adjusted odds ratio (AOR), 1.91; 95% confidence interval (CI), 1.04-3.49) whereas among women a history of unusual vaginal discharge in the past 12 months was associated with HIV infection (AOR, 1.75; 95% CI, 1.26-2.44). Young women with older partners were also at increased risk of HIV infection. Among both men and women, increasing partner numbers and inconsistent condom use were significantly associated with HIV infection. Males and females who reported participation in at least one loveLife program were less likely to be infected with HIV (AOR, 0.60; 95% CI, 0.40-0.89; AOR, 0.61; 95% CI, 0.43-0.85, respectively). CONCLUSION: This survey confirms the high HIV prevalence among young people in South Africa and, in particular, young women's disproportionate risk. Programs for youth must continue to promote partner reduction, consistent condom use and prompt treatment for sexually transmitted infections while also addressing contextual factors that make it difficult for them to implement behavior change.     

HIV/AIDS Risks among Men and Women Who Drink at Informal Alcohol Serving Establishments (Shebeens) in Cape Town,South Africa

HIV/AIDS is devastating southern Africa and the spread of HIV is fueled in some populations by alcohol use. Alcohol serving establishments, such as informal drinking places or shebeens, often serve as high-risk venues for HIV transmission. The current study examined the HIV risks of men (N = 91) and women (N = 248) recruited from four shebeens in a racially integrating township in Cape Town South Africa. Participants completed confidential measures of demographic characteristics, HIV risk history, alcohol and drug use, and HIV risk behaviors. Comparisons of 94 (28%) participants who reported meeting sex partners at shebeens to the remaining sample of shebeen goers, controlling for potential confounds, demonstrated a pattern of higher risk for HIV infection among persons who met sex partners at shebeens. Few differences, however, were observed between men (N = 47) and women (N = 47) who had met sex partners at shebeens, suggesting greater gender similarities than gender differences in this important subpopulation. These results indicate an urgent need for multi-level HIV prevention interventions targeting shebeens and the men and women who drink in these settings. National Institute of Alcohol Abuse and Alcoholism Grant R21-AA014820 supported this research.     

Gas chromatographic-mass spectrometric method for quantitation of phenylalanine and tyrosine in serum.

A validated gas chromatographic-mass spectrometric method for quantitation of phenylalanine and tyrosine in serum is described. Quantitation of phenylalanine and tyrosine with a non-labelled non-endogenous internal standard, L-2-chlorophenylalanine, compared favourably with isotope dilution mass spectrometric quantitation. The 95% reference ranges for phenylalanine. tyrosine and the phenylalanine-tyrosine molar ratio in neonate cord blood serum were determined by isotope dilution mass spectrometry and were found to be 77.1-144.7, 33.3-109.3 micromol/l and 1.1-3.0, respectively.     

Randomized Trial of a Community-based Alcohol-related HIV Risk-reduction Intervention for Men and Women in Cape Town South Africa

Background  HIV is devastating southern Africa and alcohol use is closely related to HIV transmission risks. Purpose  The current study tested the efficacy of a brief single-session HIV–alcohol risk-reduction intervention for men and women who drink at informal alcohol serving establishments (i.e., shebeens) in South Africa. Methods  A randomized community field trial recruited men (N = 117) and women (N = 236) through outreach and chain referrals. Participants received either: (a) 3-h theory-based behavioral HIV–alcohol risk-reduction intervention that focused on skills training for sexual negotiation and condom use or (b) 1-h HIV–alcohol information/education control group. Participants were followed up for 3 and 6 months post-intervention with 89% retention. Results  The risk-reduction intervention demonstrated significantly less unprotected intercourse, alcohol use before sex, numbers of sex partners, partners met at drinking establishments and greater condom use relative to the control group. However, intervention effects were moderated by alcohol use; lighter drinkers demonstrated significantly more intervention gains than heavier drinkers in the risk-reduction condition. Intervention effects occurred at 3 months follow-up and dissipated by 6 months. Conclusions  A brief HIV risk-reduction intervention reduced sexual-risk behaviors among drinkers in South Africa. However, intervention effects were weakest for those who drink heaviest. Our results provide a basis for establishing HIV prevention in alcohol serving establishments in South Africa. Research is needed to identify multi-level intervention models that can reduce risks among heavier drinkers and sustain behavior changes over time. National Institute of Alcohol Abuse and Alcoholism Grants R21-AA014820 and R01AA017399 supported this research.