Analysis of Y-STR diversity and DNA methylation variation among Black and Indian males from KwaZulu-Natal, South Africa.

Y-chromosome short tandem repeats (Y-STRs) are essential in understanding genetic structure and diversity of human populations and, most importantly, in identification of male perpetrators in criminal investigations. DNA methylation differences have been reported in human populations and methylation pattern at the CpG sites found within or flanking the Y-STR sites could also aid in human identification. Studies based on DNA methylation (DNAm) at Y-STRs are currently limited. The current study aimed to analyze the Y-STR diversity in South African Black and Indian individuals living in KwaZulu-Natal, Durban, South Africa, with the Yfiler™ Plus Kit and to analyze DNAm patterns in Y-STR markers CpG sites. DNA from 247 stored saliva samples were isolated and quantified. Across the 27 Y-STR loci in the Yfiler™ Plus Kit, 253 alleles were observed in 113 South African Black and Indian males, 112 unique haplotypes were observed, and one haplotype appeared twice (two Black individuals). No statistically significant differences were observed in the genetic diversity between the two population groups (Fst = 0.028, p-value ≥ 0.05). The kit showed a high discrimination capacity (DC) of 0.9912 and an overall haplotype diversity (HD) = 0.9995 among the sampled population groups. DYS438 and DYS448 markers displayed 2 and 3 CpG sites, respectively. Based on the two-tailed Fisher's Exact test, there were no statistically significant differences in the DNAm levels at DYS438 CpGs of Black and Indian males (p > 0.05). The Yfiler™ Plus Kit can be considered highly discriminatory among South African Black and Indian males. Studies on the South African population using Yfiler™ Plus Kit are scarce. Hence, accumulating Y-STR data on the diverse South African population will enhance the representation of South Africa in STR databases. Knowing which Y-STR markers are significantly informative for South Africa is essential for developing Y-STR kits better suited for the different ethnic groups. And to the best of our knowledge, DNA methylation analysis in Y-STR for different ethnic groups has never been done before. Complementing Y-STR data with methylation knowledge could provide population-specific information for forensic identification.

The spectrum of idiopathic inflammatory myopathies in South Africa.

INTRODUCTION: There are many reports on idiopathic inflammatory myopathies (IIM) but little information from sub-Saharan Africa. We conducted a retrospective study of IIM in a multi-ethnic cohort seen at a single centre in Durban, South Africa. METHOD: The study included patients who fulfilled the Bohan and Peter or European League Against Rheumatism/American College of Rheumatology criteria for IIM. The information recorded included demographic data, clinical findings, results of investigations, treatment and outcome. Patients with overlap myositis (OM) had myositis and criteria for another connective tissue disease. RESULTS: There were 104 patients with IIM; 82.7% female and 70.2% African blacks. They included 41 (39.4%) with OM, 26 (25%) polymyositis (PM), 26 (25%) dermatomyositis (DM), six (5.8%) juvenile dermatomyositis and five (4.8%) cancer-associated myositis. Our patients had a younger mean age at diagnosis (36.8 ± 14.7 years) compared with 45-55 years in most other studies. Scleroderma-myositis overlap accounted for 26 (63.4%) of the patients with OM. Patients with OM were significantly younger than PM (p = 0.004) and DM (p = 0.044) and had lower, but not statistically significant, creatine kinase levels at diagnosis compared with PM (p = 0.052) and DM (p = 0.073). Interstitial lung disease was more common in OM (p = 0.001) and PM (p = 0.024) than DM. Oropharyngeal weakness was more common in DM than OM (p = 0.001) and PM (p = 0.032). African blacks were younger (p = 0.028) at diagnosis and had more cardiac abnormalities (p = 0.034) than Indians. CONCLUSION: The spectrum of IIM in our cohort of mainly African blacks is similar to other studies, with OM being the most frequent subtype. Key Points • As there is limited information on idiopathic inflammatory myopathies (IIM) in sub-Saharan Africa, this study reports the spectrum of IIM in a South African cohort of predominantly African blacks. • Our patients were younger at diagnosis, and overlap myositis was the most common phenotype. • Comparisons with other studies show similarities in the manifestations of IIM.

[Selective laser trabeculoplasty in African blacks]. / Trabéculoplastie sélective chez le mélanoderme africain.

INTRODUCTION: The treatment of primary open angle glaucoma (POAG) is preferably medical. However, when medical therapy fails, alternative or complementary treatments may be considered. In this regard, selective laser trabeculoplasty is a widely popular procedural treatment whose accepted benefits have been very little studied in African blacks. The objective of this study was to assess the efficacy of selective laser trabeculoplasty on the reduction of intraocular pressure (IOP) in African blacks with POAG. METHODS: We conducted a retrospective study of black patients treated with selective laser trabeculoplasty between March 2010 and March 2011. All patients had POAG with trabecular meshwork accessible over 360°. The treatment protocol consisted of a 360°treatment in two sessions (180°/session) 15 days apart. Success was defined as decrease from the initial IOP≥3mm Hg without additional medications. RESULTS: We included 44 patients, corresponding to 82 eyes. The mean age of the patients was 55.94±11.66 years with extremes of 19 years and 76 years. The mean intraocular pressure before laser treatment (initial IOP) was 18.43±4.81mm Hg. After laser treatment, the mean pressure reduction was (i) 3.81mm Hg (20.67%) at 15 days ; (ii) 4.08mm Hg (22.14%) at 1 month; (iii) 4.45mm Hg (24.14%) at 3 months; and (iv) 4.95mm Hg (26.86%) at 6 months. The success rate after laser treatment was 67.60% at 15 days, 83.78% at 1 month, 72.09% at 3 months and 80.43% at 6 months. CONCLUSION: Selective laser trabeculoplasty is effective in African blacks. Its efficacy is comparable to that of a carbonic anhydrase inhibitor or even a prostaglandin. It could be a complementary or substitutive alternative to POAG medications in African blacks.

The clinical manifestations and response to treatment in South Africans with lupus nephritis.

There are varying observations on the influence of ethnicity on the clinical spectrum and response to treatment in lupus nephritis (LN). We studied a multiethnic South African LN cohort to determine the clinical manifestations, histological involvement and response to therapy. We reviewed the records of LN patients at Inkosi Albert Luthuli Central Hospital in Durban. There were 105 patients, 92.5% females and they comprised 49.1% Indians and 45.3% African Blacks. The mean age was 31.3 ± 12.5 years, and 41.5% had LN at first presentation of lupus. The most common histological classes were Class V alone in 34.9%, Class IV (± Class V) in 25.5% and Class III (±Class V) in 22.6%. The estimated glomerular filtration rate was reduced (<30 ml/min) at presentation in 15 (14.2%). Eighty-seven patients received therapy for LN. A response to induction therapy was noted in 81.6% and maintenance therapy (12 months) in 73.6%. Response to mycophenolate mofetil (MMF) was 80.4% and 68.4% during induction and maintenance therapy, respectively. There was no ethnic difference in the histological class or response to MMF but African Blacks had more severe renal disease at presentation. In conclusion, our multiethnic LN cohort shows a high prevalence of membranous LN and good response to treatment.

Comparison of ethnicity, gender, age of onset and outcome in South Africans with systemic lupus erythematosus.

Ethnicity, gender and age of onset are reported to influence the expression and outcome of systemic lupus erythematosus. We studied a multi-ethnic cohort of 408 South Africans (91.2% females) comprising 237 (58.1%) Indians, 137 (33.6%) African Blacks, 17 (4.2%) Mixed ethnicity and 17 (4.2%) Whites. The most common manifestations were arthritis (80.6%), photosensitivity (67.2%), oral ulcers (50.0%), malar rash (49.0%) and renal (39.2%). The common laboratory findings were positive anti-nuclear factor (96.8%), haematological (74.8%) and anti-dsDNA antibodies (45.3%). Serositis ( p = 0.002), nephritis ( p = 0.039), leucopaenia ( p = 0.001), haemolytic anaemia ( p = 0.026), anti-dsDNA antibodies ( p = 0.028) and anti-Sm antibodies ( p = 0.050) were more common in African Blacks compared to Indians. Males had increased prevalence of discoid rash ( p = 0.006) and anti-Sm antibodies ( p = 0.016). Discoid rash ( p = 0.018), renal involvement ( p < 0.001), psychosis ( p = 0.028), seizures ( p = 0.020), anti-dsDNA antibodies ( p = 0.009), leucopaenia ( p = 0.006), haemolytic anaemia ( p = 0.017) and thrombocytopaenia ( p = 0.023) were more common with early-onset systemic lupus erythematosus. On multivariate analysis, the independent predictors of death were renal involvement, anti-dsDNA antibodies and seizures. There were 53 (13%) deaths and the five- and 10-year survival was 90.8% and 85.7% respectively, with no differences related to ethnicity or age of onset. In conclusion, we report on the spectrum and outcome of systemic lupus erythematosus in a large South African multi-ethnic cohort.

Serum ferritin concentration is affected by ferroportin Q248H mutation in Africans.

BACKGROUND: Ferroportin Q248H mutation is common in populations with African ancestry. Studies have reported that the mutation does not alter the ferroportin-hepcidin axis, but there is evidence suggesting that the mutation may lead to hyperferritinemia. We report on the relationship of ferroportin Q248H mutation on serum ferritin (SF) in health adults. SUBJECTS AND METHODS: A total of 174 apparently healthy adults from Botswana were studied. SF was measured using an enzyme immunoassay and ferroportin Q248H mutation was identified by polymerase chain reaction and restriction enzyme digestion. Independent sample Mann-Whitney U test was used to correlate the presence of the mutation with SF. RESULTS: Ferroportin Q248H mutation was identified in 30 individuals (17.2%) (one homozygote, 29 heterozygotes) and was absent in 144 individuals (82.8%), with Q248H allele frequency of 8.9%. In males, SF was significantly higher in ferroportin Q248H heterozygotes compared to wild types, p=0.029, but the relationship between ferroportin Q248H mutation and iron stores was blunted in females. CONCLUSION: Our study of healthy adults provides further evidence that ferroportin Q248H mutation affects SF concentration in Africans.

Sex determination by discriminant function analysis of lumbar vertebrae.

Sex determination is critical for developing the biological profile of unidentified skeletal remains. When more commonly used elements (os coxa, cranium) for sexing are not available, methods utilizing other skeletal elements are needed. This study aims to assess the degree of sexual dimorphism of the lumbar vertebrae and develop discriminant functions for sex determination from them, using a sample of South African blacks from the Raymond A. Dart Collection (47 males, 51 females). Eleven variables at each lumbar level were subjected to univariate and multivariate discriminant function analyses. Univariate equations produced classification rates ranging from 57.7% to 83.5%, with the highest accuracies associated with dimensions of the vertebral body. Multivariate stepwise analysis generated classification rates ranging from 75.9% to 88.7%. These results are comparable to other methods for sexing the skeleton and indicate that measures of the lumbar vertebrae can be used as an effective tool for sex determination.

Acute presentation of thrombocytopaenia in systemic lupus erythematosus is associated with a high mortality in South Africa.

The objective of this study was to determine the pattern of presentation, response to treatment, and outcome in patients with systemic lupus erythematosus (SLE) and thrombocytopaenia (TCP). A retrospective review of the records of patients with SLE and TCP and a matched control group of SLE patients without TCP, seen in the rheumatology department in Durban, South Africa, was performed. The demographic data, clinical findings, laboratory findings, treatment and outcome were recorded. There were 54 patients and an equal number of controls. They comprised 30 Indians and 24 African Blacks, median age of 33 years and female to male ratio 5.8:1. A group of eight patients who initially presented with idiopathic thrombocytopaenic purpura (ITP) and subsequently developed SLE were analysed separately. An acute presentation was noted in 31 patients (57%). Patients with an acute presentation had an increased prevalence of renal disease (77% vs 43.5%; p=0.01) and an increased number of deaths (38.7% vs 4.4%; p=0.004). The majority of patients responded to corticosteroids (68.5%) and splenectomy. There was an increased prevalence of renal disease (p=0.03) and deaths (p=0.004) among patients with TCP. The majority of deaths had an acute presentation ((12/13; 92.3%) (p=0.004)), and were due to infection and active lupus. TCP with an acute presentation is associated with a high mortality and predicts survival in SLE.