Ernest Song

Ethnic differences in allelic associations of the interleukin-1 gene cluster in South African patients with inflammatory bowel disease (IBD) and in control individuals.

Abstract. The allelic frequencies of TaqI, PstI, and variable number of tandem repeat (VNTR) polymorphisms of the IL-1β, IL-1 receptor (IL-1Re), and IL-1 receptor antagonist (IL-1Ra) respectively, were investigated in black and white patients with inflammatory bowel diseases (IBD) and compared with control individuals. Plasma concentrations of IL-1β and IL-1Ra were also determined in these individuals. The IL-1β TaqI(–) allele was significantly more frequent in 50 white IBD patients (60%) compared with 47 white controls (17%), and 20 black patients (20%) (P=0.00001 and P=0.0001, respectively). The IL-1Re PstI(–) allele was significantly more frequent in 20 black patients (75%) compared with 50 white patients (44%) (P=0.0001). The frequency of the IL-1Ra 240-bp allele was lower in black (12%) compared with white controls (25%), (P=0.0151), and the 410-bp allele was more frequent in black (87%) compared with white (73%) controls (P=0.0096). Linkage disequilibrium was found in black individuals homozygous for the 410-bp allele of IL-1Ra, and the PstI(–) allele of IL-1Re (84%) (P=0.0032). There was a significantly increased level of IL-1Ra in black patients compared with white patients and black controls (P=0.0006 and P=0.0008, respectively). The population differences in allelic frequencies of the IL-1 gene cluster and IL-1Ra concentrations suggest that genetic and environmental factors play an important role in susceptibility to IBD.

Recombinant leucocyte interferon treatment of chronic hepatitis B: An analysis of two therapeutic trials

We have investigated the efficacy of recombinant alpha-interferon treatment of chronic hepatitis B virus (HBV) infection in two therapeutic trials. Forty-four patients positive for HBsAg, HBeAg, DNA polymerase and HBV-DNA were studied. Fourteen carriers were treated in the first trial with doses ranging from 18 to 50 million units (mu)/m2 3 times per week. Six of 14 treated carriers (43%) have a sustained loss of HBeAg, HBV-DNA and DNA polymerase. Four lost HBsAg (29%). Two of 11 (18%) untreated carriers lost HBeAg, but none lost HBsAg (P = 0.05). Nineteen patients were entered in a second trial to assess dose response. Fourteen were treated with doses ranging from 2.5 to 10 mu/m2. Five patients were untreated. Two treated patients seroconverted to anti-HBe, and a third cleared HBsAg and seroconverted to anti-HBs. None of the controls was anti-HBe-positive. Thus 9/28 (32%) carriers have lost replicating HBV versus 2/16 (13%) of untreated patients. Elevated pretreatment serum ALT concentrations and severe chronic active hepatitis were associated with inhibition of viral replication in treated patients suggesting that seroconversion may require an appropriate host response. The efficacy of recombinant interferon is restricted, but it may be of benefit in a proportion of carriers.

Frequent detection of hepatitis B virus variants associated with lamivudine resistance in treated South African patients infected chronically with different HBV genotypes

This retrospective study investigated and characterized the YMDD motif of the hepatitis B virus (HBV) reverse transcriptase (RT) gene, in sequential samples of 17 South African patients with chronic hepatitis B infection on lamivudine treatment. The profile of HBV genotypes as well as the genetic variability of pre‐core (pre‐C) and basal core promoter regions (BCP) were also determined in these patients. Mutations within the RT gene were determined by direct sequencing using SpectruMedix SCE 2410 genetic analyzer and INNO‐LiPA HBV DR (Innogenetics), while the genetic variability of the pre‐C/BCP and surface gene were determined by direct sequencing only. HBV genotypes were determined by analysis of the surface, core and RT genes using a web‐based genotyping tool (NCBI). HBV DNA was quantified using Cobas Amplicor HBV Monitor assay (Roche Diagnostics). Of the 17 patients, 13 (76.5%) carried YMDD mutations: 7 with rtM204I (2 HBeAg‐positive and 5 HBeAg‐negative) and 6 with rtM204V (4 HBeAg‐positive and 2 HBeAg‐negative). Of the 13 patients with resistant HBV strains, 8 (61.5%) carried genotype A, 3 (23%) genotype B, and 2 (15.3%) genotype C. Overall, only 5 of 13 (38%) patients with YMDD mutations experienced genotypic viral drug resistance and treatment failure. Of the 17 patients, 3 carried both pre‐C (G1896A) and BCP (A1762T/G1764A) mutants, 1 pre‐C only and 1 BCP only. This study demonstrated frequent detection of mutations associated with lamivudine‐resistance in therapy‐experienced South African patients infected chronically with different HBV genotypes, and confirmed that these mutations are not always accompanied by clinical relapse. J. Med. Virol. 81:996–1001, 2009.

Differences in the prevalence of a TaqI RFLP in the 3‘ flanking region of the α1-proteinase inhibitor gene between asthmatic and non-asthmatic black and white South Africans

The prevalence of the Taq I(‐) allele in variants of α1‐proteinase inhibitor (α1PI) was investigated in a group of 28 black asthmatic patients and 32 black control individuals, and was compared to 43 white asthmatic patients and 32 white control individuals. The plasma concentration of α1PI was determined in eight black and 14 white asthmatics without the Taq I(‐) allele, and compared to seven black and three white asthmatics with the Taq I(‐) allele. Alpha‐1‐PI concentration was also determined in 10 black and 29 white control individuals without the Taq I(‐) allele and compared to seven black and three white controls with the Taq I(‐) allele. There was a highly significant difference in the frequency of the Taq I(‐) allele between black South Africans (24.1%) and white South Africans (6%) (p<0.00001) and a significant difference in the frequency of the Taq I(‐) allele between black asthmatics and white asthmatics (p = 0.0004) and between black controls and white controls (p = 0.011). The Taq I(‐) allele was significantly associated with the Ml(Val213) variant as compared to the Ml (Ala213) of α1PI (p = 0.0042). There was no difference in the concentration of α1PI between the asthmatics (black and white) lacking the Taq I(‐) allele and the asthmatics (black and white) with the allele. However, a significant increase in plasma α1PI concentration was found in the asthmatics compared to the controls (p = 0.011). The Taq I(‐) allele did not seem to interfere with the basal expression of α1PI in the groups of asthmatic patients in this study.

The role of increased gastrointestinal alcohol production in patients with the metabolic syndrome: Implications for the pathogenesis of non-alcoholic fatty liver disease

Aim. Explore the possibility that increased gastrointestinal alcohol production may play a role in the pathogenesis of non-alcoholic fatty liver disease in patients with the metabolic syndrome. Methods. Blood, urine and breath levels of alcohol measured in 20 patients with the metabolic syndrome were compared with those of 20 matched healthy controls. Results. Eighty per cent of the patients had dyslipidaemia, 60% systemic hypertension and 70% type 2 diabetes mellitus. Seventy five per cent had ultrasonographic features of fatty liver disease, with mean serum aminotransferase activities being significantly higher in the patients than in the controls, alanine aminotransferase (ALT) 57.4±44.79 U/l versus 17.4±4.60 U/l (95% CI 18.02–61.42, p<0.001), and aspartate aminotransferase (AST) 52.5±36.21 U/l versus 23.4±4.86 U/l (95% CI 11.99–46.20, p<0.01). Adiponectin levels were lower (6 875 versus 15 475 ng/l; median value, p<0.01) in the patients with the metabolic syndrome and leptin levels significantly higher (13.56 versus 3.05 ng/l; median value, p<0.05). Alcohols were detected in body fluids of 60% of the patients, of which 35% tested positive for ethanol, 55% tested positive for methanol, and 30% tested positive for both. None of the controls tested positive for any alcohols. Conclusions. Endogenous alcohol production may be involved in the pathogenesis of non-alcoholic fatty liver disease in patients with the metabolic syndrome.