Renin-angiotensin system and associated gene polymorphisms in myocardial infarction in young South African Indians.

The renin-angiotensin system plays an important role in cardiovascular regulation. Abnormalities in genetic components of this system, such as the angiotensin-converting enzyme (ACE) gene, angiotensin II type 1 (AT1) receptor gene and angiotensinogen (AGT) gene, may cause a variety of adverse cardiovascular effects. It was the aim of this study, therefore, to investigate the involvement of the ACE insertion/deletion (I/D), AT1 receptor 1166 A->C and AGT M235T polymorphisms as predisposing factors for myocardial infarction (MI) in 195 young South African Indians (C AT1 receptor polymorphism with respect to both genotype and allelotype (p > 0.70), or in the genotype or allele frequency distribution of the AGT M235T polymorphism (p > 0.44). However, a significant in crease was noted for both the AT1 receptor C variant (p = 0.025) and the AGT T variant (p = 0.047) in hypertensive patients compared with those who were normotensive. In conclusion, results of this study indicate that the ACE I/D, the 1166 A->C AT1 receptor and AGT M235T polymorphisms do not confer any increased risk for MI in young South African Indians.

P53 codon 72 polymorphism and human papillomavirus type in relation to cervical cancer in South African women.

The usefulness of the arginine (Arg) residue at codon 72 of the p53 tumor suppressor gene as a marker for the risk of cervical cancer remains unclear. Studies to date have focused mainly on Caucasian subjects despite marked ethnic variations in both the p53 polymorphism and the frequency of cervical carcinoma. Furthermore, not all studies have taken into account the type of human papillomavirus (HPV) infection present. In this study, undertaken at King Edward VIII Hospital, Durban, South Africa, we determined the p53 codon 72 status in 281 black South African women with cervical cancer and 340 ethnically matched healthy control subjects. In addition, HPV DNA was confirmed in 190 cervical tumors and the viral type determined. Results showed that overall more cancer patients than control subjects had an Arg allele at codon 72 with respect to both genotype and allelotype (P < 0.05). A significantly higher (P < 0.001) Arg allele frequency (55%) was also observed in patients whose tumors contained low or intermediate risk HPV DNA compared with control subjects (31%); the Arg homozygosity rate was 34% and 9% in patients and controls, respectively (P < 0.001). In contrast, patients harboring HPV 16/18 infections showed no differences in p53 status compared with controls. It would appear that, in the absence of HPV 16/18 infections, the Arg allele at codon 72 of the p53 tumor suppressor gene may constitute a risk factor for carcinogenesis of the cervix.

Apolipoprotein E polymorphism in South African Zulu women with preeclampsia.

OBJECTIVES: Apolipoprotein E may contribute to the hypertiglyceridemia and consequent endothelial dysfunction of preeclampsia. We carried out a study to determine whether the apolipoprotein E genotype plays any role as a risk factor for preeclampsia in a black South African population with a high incidence of preeclampsia. DESIGN: A descriptive, prospective study design was used. SETTING: King Edward VIII Hospital, a tertiary care, referral academic hospital in Durban, South Africa. PATIENTS AND PARTICIPANTS: One hundred three South African Zulu women with preeclampsia and 110 healthy normotensive women attending the antenatal clinic were recruited. MAIN OUTCOME MEASURES: The relationship between the apolipoprotein E allele and genotype frequencies to preeclampsia as well as adverse perinatal outcome. RESULTS: The frequencies of varepsilon2 and varepsilon4 alleles (0. 19 and 0.25, respectively) were much higher than those reported in other population groups. However, there was no significant difference in the apolipoprotein E genotype and allele frequencies between the study and the control groups. The varepsilon2/2 genotype was associated with increased risk of perinatal death (p = 0.047). CONCLUSION: The study suggests that, despite the high incidence of both preeclampsia and the varepsilon2 and varepsilon4 alleles in South African Zulu women, apolipoprotein E genotype does not appear to be a risk factor for preeclampsia in this population.

5,10 methylenetetrahydrofolate reductase polymorphism in black South African women with pre-eclampsia.

The polymorphic C677T mutation in the gene encoding 5,10 methylenetetrahydrofolate reductase has been shown to be a risk factor for pre-eclampsia in Japanese and European women when inherited as a homozygous trait. We attempted to verify these findings in a black African population with a high incidence of pre-eclampsia. No difference in frequency of the T-allele was observed in 105 women with pre-eclampsia, compared with 110 healthy pregnant normotensive women. Only one woman with pre-eclampsia was TT homozygous, suggesting that methylenetetrahydrofolate reductase polymorphism is not an important factor in the pathogenesis of pre-eclampsia in black South African women.

PIP: This study aims to determine whether the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) polymorphism plays any role as a risk factor for preeclampsia in black South African women. A total of 105 pregnant women with preeclampsia were included in the study and were subjected to several tests. Test results showed that the MTHFR genotypes and allele frequencies in the study group and control group have no significant difference in the frequencies of the homozygous TT genotype or the T-allele. Among the respondents, only one woman with preeclampsia was homozygous for the C677T mutation. Findings indicate that preeclampsia in black South African women affects 18% of pregnancies. In addition, the C677T mutation cannot be considered an important factor in the pathogenesis of preeclampsia in this study population. Further studies are required for clarifications concerning these issues.

Molecular diagnosis of multiple endocrine neoplasia type 2A.

OBJECTIVE: To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. SUBJECTS: A three-generation kindred with clinically and biochemically diagnosed medullary thyroid cancer. METHOD: Identification of a heterozygote mutation by nucleic acid sequencing and restriction analyses. RESULTS: A heterozygote T-->C (Cys-->Arg) mutation at codon 618 in exon 10 of the RET proto-oncogene was identified in 4 family members who had previously been diagnosed with medullary thyroid cancer. The same mutation was also found in one of the proband's presymptomatic children who subsequently underwent a pre-emptive thyroidectomy. The genetic diagnosis was confirmed by histology. No mutations were detected in any other family members. CONCLUSION: Identification of heterozygote germline mutations in multiple endocrine neoplasia is direct, highly accurate and cost-effective. This study demonstrates that, appropriately used, molecular diagnosis can supersede conventional biochemical methods in the management of patients with inherited cancers.

Variations in c-erbB-2 proto-oncogene status in breast cancer tumors as detected by two different cDNA probes.

We examined 232 breast carcinomas for c-erbB-2 amplification by Southern analysis using two different cDNA probes. Using these same probes, 95 of these tumors were also examined for mRNA expression by Northern analysis. Amplification was detected in 20 and 17% of the tumors with the probes pHER 2 and pCER 204, respectively, but only 10% showed amplification with both probes. A significantly higher incidence (p < 0.01) of mRNA overexpression was detected with the pHER 2 probe (34%) compared with the pCER 204 probe (16%), with only 11% of tumors demonstrating overexpression with both probes. A total of 10 tumors (11%) exhibited amplification as well as overexpression with pHER 2, whereas significantly fewer (3%) manifested both abnormalities with the larger pCER 204 probe (p < 0.05). Amplification of c-erbB-2, as detected with the pHER 2 probe but not with the pCER 204 probe, was significantly associated with the absence of both estrogen and progesterone receptors (p < 0.05 and p < 0.01, respectively). No relationship was found with other clinical prognostic indicators, such as nodal involvement and metastases. As determined by either probe, overexpression was not associated with prognostic indicators. There was no significant difference in the c-erbB-2 status of tumors from different racial groups.