Significance of dietary folate intake, homocysteine levels and MTHFR 677 C>T genotyping in South African patients diagnosed with depression: test development for clinical application.

Low folate intake in the presence of the functional MTHFR 677 C > T (rs1801133) polymorphism is an important cause of elevated homocysteine levels previously implicated in major depressive disorder (MDD) and many other chronic diseases. In this study the clinical relevance and inter-relationship of these aspects were evaluated in 86 South African patients diagnosed with MDD and 97 population-matched controls participating in a chronic diseases screening program. A questionnaire-based clinical and nutrition assessment was performed, homocysteine levels determined, and all study participants genotyped for MTHFR 677 C > T (rs1801133) using allele-specific TaqMan technology. The folate score was found to be significantly lower in the patient group compared to controls (p = 0.003) and correlated with increased body mass index (BMI), particularly in females with MDD (p = 0.009). BMI was significantly higher in the MDD patients compared with controls after adjustment for age and sex (p = 0.015), but this association was no longer significant after further adjustment for the level of folate intake in the diet. In MDD patients but not controls, the minor T-allele of MTHFR 677 C > T was associated with increased BMI (p = 0.032), which in turn correlated significantly with increased homocysteine levels. The significant association between BMI and homocysteine levels was observed in both the MDD patient (p = 0.049) and control (p = 0.018) study groups. The significantly higher homocysteine levels observed in MDD patients compared to controls after adjustment for age and sex (p = 0.030), therefore appears to be mediated by the effects of MTHFR 677 C > T and low folate intake on BMI. Detection of the low-penetrance MTHFR 677 C > T mutation reinforces the importance of folate intake above the recommended daily dose to prevent or restore dysfunction of the methylation pathway.

The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors.

UNLABELLED: The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene. AIM: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism. Homocysteine levels were measured in a subgroup of 60 patients and 87 controls screened for multiple vascular risk factors. After adjustment for potential confounders, the risk-associated FTO rs9939609 A-allele was associated with raised homocysteine levels (p = 0.003) in patients diagnosed with MS, but not in controls. Homocysteine levels correlated positively with body mass index (BMI) (p = 0.045) and total cholesterol levels (p = 0.048). Both homocysteine (p = 0.011) and BMI (p = 0.017) were significantly reduced with higher intake of folate in the diet. Higher BMI also correlated with increased intake of saturated/trans fat (p < 0.01) and low physical activity (p < 0.006). Daily intake of at least five fruits and vegetables had a favourable lowering effect on the Expanded Disability Status Scale (EDSS) (p = 0.035), while smoking increased MS disability (p < 0.001). This study has shown for the first time that having a diagnosis of MS moderates the effect of the FTO rs9939609 polymorphism on homocysteine levels. This is consistent with the role of FTO in demethylation and epigenetic changes. Identification of FTO rs9939609 reinforces the importance of adequate fruit, vegetable and folate and restriction of saturated/trans fat intake in the diet.

CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application.

Approximately 25% of clinically important drugs and numerous environmental carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. In this study we determined the appropriateness of adding CYP2D6 genotyping to the breast cancer genetic testing options already available in South Africa, which include BRCA mutation screening and transcriptional profiling to assess estrogen receptor (ER) status. A total of 114 South African breast cancer patients, including 52 Caucasian and 62 Coloured (Mixed ancestry), and 63 Caucasian control individuals were genotyped for the most common inactivating allele (CYP2D6*4, rs3892097) previously identified in the CYP2D6 gene. In the initial validation data set consisting of 25 Caucasian and 62 Coloured patients, the CYP2D6*4 allele frequency was significantly higher in Caucasian compared to Coloured patients (24% vs. 3%, p<0.001), similar to previous findings in the general South African population. Extended CYP2D6 genotyping was subsequently performed in an implementation data set of 27 Caucasian breast cancer patients, to determine the prevalence of depression and use of antidepressants in a clinical setting. A medical history of depression and/or use of antidepressants was reported in 37% (10/27) of these breast cancer patients genotyped for CYP2D6*4. This translational research study has led to increased awareness among clinicians of the potential benefits of CYP2D6 genotyping to facilitate prevention of cumulative risk in a high-risk genetic subgroup of breast cancer patients considered for concomitant treatment of TAM and antidepressants that may reduce enzyme function.

A biobank to support HIV malignancy research for sub-Saharan Africa.

Sub-Saharan Africa has one of the highest incidences of infection with HIV globally, but more people in this region are living longer owing to increased access to antiretroviral therapy. However, along with increased care and treatment, this population is expected to have an increase in HIV-associated cancers, as is being seen in the USA and other developed countries. To support translational research in HIV-associated cancers, Stellenbosch University in Cape Town, South Africa, was funded to house the state-of-the-art AIDS and Cancer Specimen Resource Sub-Saharan Africa Regional Biorepository (SSA RBR) to proactively obtain, manage and process biospecimens and associated clinical data representing both AIDS-defining and non-AIDS-defining cancers for research. The SSA RBR furthermore functions as the biorepository for AIDS Malignancy Consortium sub-Saharan clinical trial activities in this region. Although the site had much experience with cryopreservation and storage of specimens, capacity building revolving around operations under International Society for Environmental and Biological Resources/National Cancer Institute best practices took place in such areas as custodianship v. ownership, data sharing and facilities management. The process from selection until launch took 14 months.

Capillary activity of surgical sutures and suture-dependent bacterial transport: a qualitative study.

OBJECTIVE: To evaluate the multitude of new synthetic absorbable sutures (both monofilament and multifilament) in comparison with older materials with regard to capillarity and bacterial transport. METHODS: Sutures of United States Pharmacopoeia (USP) 4-0 thickness were arranged in a three-chamber system under sterile conditions. Either a colorant (liquid transport evaluation) or bacteria (bacterial transport evaluation) were added to the contamination chamber, and movement of colorant or bacteria was evaluated for as long as 30 days. RESULTS: None of the monofilament sutures transported colorant or bacteria. Colorant transport was found on the pseudomonofilament and multifilament sutures between the first and the fifth day. Escherichia coli were transported on the majority of the multifilament sutures, although no transport was found on silk or polyester sutures. Bacterial transport was most often evident in tests using the motile Proteus mirabilis. CONCLUSIONS: All multifilament and pseudomonofilament suture designs allowed transport of colorants and bacteria to some degree. The movement of fluids and bacteria did not depend on the absorptive capacity of the sutures, coating, or the presence of an open suture end.