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George Ghartey-Kwansah Johnson N. Boampong Benjamin Aboagye Richmond Afoakwah Elvis O. Ameyaw 《Hemoglobin》2016,40(1):32-37
Thalassemia and sickle cell disease constitute the most monogenic hemoglobin (Hb) disorders worldwide. Clinical symptoms of α+-thalassemia (α+-thal) are related to inadequate Hb production and accumulation of β- and/or γ-globin subunits. The association of thalassemia with malaria remains contentious, though from its distribution it appears to have offered some protection against the disease. Data on the prevalence of thalassemia in Ghana and its link with malaria is scanty and restricted. It was an objective of this cross-sectional study to determine the prevalence of thalassemia in areas representing two of Ghana’s distinct ecological zones. The relationship between thalassemia and Plasmodium falciparium (P. falciparum) infection was also ascertained. Overall, 277 patients presenting to health facilities in the study areas were recruited to participate. Tests were carried out to determine the presence of α+-thal, sickle cell and malaria parasites in the blood samples of participants. The outcome of this study showed an α+-thal frequency of 19.9% for heterozygotes (?α/αα) and 6.8% for homozygotes (?α/?α). Plasmodium falciparum was detected in 17.7% of the overall study population and 14.9% in those with α+-thal. No association was observed between those with α+-thal and the study sites (p?>?0.05). A test of the Hardy-Weinberg law yielded no significant difference (p?0.001). Findings from this study suggest a modest distribution of α+-thal in Ghana with no bias to the ecological zones. Although the prevalence and parasite density were relatively low in those with the disorder, no association was found between them. 相似文献
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Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals 总被引:13,自引:0,他引:13
McLeod HL Pritchard SC Githang'a J Indalo A Ameyaw MM Powrie RH Booth L Collie-Duguid ES 《Pharmacogenetics》1999,9(6):773-776
Thiopurine methyltransferase (TPMT) degrades 6-mercaptopurine, azathioprine and 6-thioguanine which are commonly used in the treatment of autoimmune diseases, leukaemia and organ transplantation. TPMT activity is polymorphic as a result of gene mutations. Heterozygous individuals have an increased risk of haematological toxicity after thiopurine medication, while homozygous mutant individuals suffer life threatening complications. Previous population studies have identified ethnic variations in both phenotype and genotype, but limited information is available within African populations. This study determined the frequency of common TPMT variant alleles in 101 Kenyan individuals and 199 Caucasians. The frequency of mutant alleles was similar between the Caucasian (10.1%) and Kenyan (10.9%) populations. However, all mutant alleles in the Kenyan population were TPMT*3C compared with 4.8% in Caucasians. In contrast TPMT*3A was the most common mutant allele in the Caucasian individuals. This study confirms ethnic differences in the predominant mutant TPMT allele and the findings will be useful for the development of polymerase chain reaction-based strategies to prevent toxicity with thiopurine medications. 相似文献
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Thymidylate synthase (TS) regulates the production of DNA synthesis precursors and is an important target of cancer chemotherapy. A polymorphic tandem repeat sequence in the enhancer region of the TS promoter was previously described, where the triple repeat gives higher in vitro gene expression than a double repeat. We recently identified ethnic differences in allele frequencies between Caucasian and Asian populations. We now describe assessment of genotype and allele frequencies of the TS polymorphism in 640 African (African American, Ghanaian and Kenyan) and Caucasian (UK, USA) subjects. The double and triple repeat were the predominant alleles in all populations studied. The frequency of the triple repeat allele was similar between Kenyan (49%), Ghanaian (56%), African American (52%), American Caucasian (54%) and British Caucasian (54%) subjects. However, two novel alleles contained 4 and 9 copies of the tandem repeat. These novel alleles were found at a higher allele frequency in African populations (Kenyan 7%, Ghanaian 3%, African American 2%) than Caucasians (UK 1%, USA 0%). The novel alleles identified in this study decrease in frequency with Western migration, while the common alleles are relatively stable. This is a unique example suggesting the influence of multiple selection pressures within individual populations. Hum Mutat 16:528, 2000. 相似文献
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Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits
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Samuel Kyei George Asumeng Koffuor Paul Ramkissoon Elvis Ofori Ameyaw Emmanuel Akomanin Asiamah 《国际眼科》2016,9(4):528-535
AIM: To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits.
METHODS: Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed.
RESULTS: The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells.
CONCLUSION: The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators. 相似文献
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Thiopurine methyltransferase alleles in British and Ghanaian populations 总被引:12,自引:0,他引:12
Ameyaw MM; Collie-Duguid ES; Powrie RH; Ofori-Adjei D; McLeod HL 《Human molecular genetics》1999,8(2):367-370
Thiopurine methyltransferase (TPMT) catalyses the S-methylation of
thiopurine drugs such as 6-mercapto-purine, 6-thioguanine and azathioprine.
TPMT activity is inherited as an autosomal co-dominant trait, and several
mutations in the TPMT gene have been identified which correlate with a low
activity phenotype. Although ethnic differences in TPMT activity have been
described, population frequency analysis of TPMT alleles has not been well
defined in different ethnic groups. The frequency of four allelic variants
of the TPMT gene, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were compared in
British Caucasian (n = 199) and Ghanaian (n = 217) populations using
PCR-RFLP and allele- specific PCR-based assays. TPMT*3C was found in 14.8%
of Ghanaians (31 heterozygotes, one homozygote). The TPMT*2, TPMT*3A and
TPMT*3B alleles were not detected in any of the Ghanaian samples analysed.
In contrast, 10.1% of British subjects had variant alleles, consisting of
TPMT*2 (n = 2), TPMT*3A (n = 17) and TPMT*3C (n = 1) alleles. The
frequencies of mutant alleles in this study were 5.3 and 7.6% in British
Caucasians and Ghanaians, respectively. Among Ghanaian tribes, Ewe subjects
had a lower frequency of mutant alleles (5.9%) than Ga (13.2%) or Fanti
(11.6%), although this did not reach statistical significance. This study
provides the first analysis of TPMT mutant allele frequency in an African
population and indicates that, unlike Caucasians, TPMT*3C is the most
common allele in African subjects.
相似文献
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Catechol-O-methyltransferase (COMT) catalyses the O-methylation of neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Ethnic differences in COMT activity have been observed in several populations. Previous studies suggest that the g1947G>A low activity allele is less common in individuals of African origin. COMT genotyping was performed using a mini-sequencing method in 195 healthy Ghanaians with a frequency of the homozygous g1947G>A of 6%. This study provides confirmation that the low activity COMT allele is less common in individuals of African origin. This finding may be important clinically with regards to the treatment of many neuropsychiatric disorders and in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression and hypertension. 相似文献
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c-erbB-2 is not a major factor in the development of colorectal cancer 总被引:19,自引:0,他引:19
McKay JA Loane JF Ross VG Ameyaw MM Murray GI Cassidy J McLeod HL 《British journal of cancer》2002,86(4):568-573
We have investigated c-erbB-2 protein expression in a large cohort of well-characterized colorectal tumours, and in a subset of lymph node metastases. We have also evaluated a Val(655)Ile single nucleotide polymorphism, which is associated with an increased risk of breast cancer, in a subset of the colorectal cancer patients and in healthy control subjects. Immunohistochemical studies revealed that while 81.8% of tumours expressed c-erbB-2, in the majority of cases equivalent levels of c-erb-B2 were seen in adjacent normal mucosa. Colon tumours were significantly more likely to express c-erbB-2 than rectal tumours (P=0.015). Only 52.4% of the metastases displayed staining patterns concordant with their primary tumour, indicating that determination of c-erbB-2 protein in colorectal tumours cannot predict the status of lymph node metastases. PCR--RFLP analysis of the Val(655)Ile single nucleotide polymorphism demonstrated that allele frequencies were identical between colorectal cancer patients and a control group of Caucasian subjects (Ile=0.80 and Val=0.20 in each case), indicating that it is not related to the risk of developing colorectal cancer in this population. Furthermore, there was no relationship between c-erbB-2 protein expression and gene polymorphism (P=0.58). In terms of prognosis, no association was seen between either c-erbB-2 protein expression or the presence of the Val allele and patient survival (P>0.05 in each case), suggesting that c-erbB-2 is not a prognostic marker in colorectal cancer. 相似文献
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Maxwell TJ Ameyaw MM Pritchard S Thornton N Folayan G Githang'a J Indalo A Tariq M Mobarek A Evans DA Ofori-Adjei D Templeton AR McLeod HL 《International journal of molecular medicine》2005,16(4):573-580
The human beta-2 adrenergic receptor (beta2AR) is responsible for the binding of endogenous catecholamines and their exogenously administered agonists and antagonists. Three functional polymorphisms in codons 16, 27 and 164 have been described which have clinical importance for several diseases, including asthma, hypertension, heart failure, cystic fibrosis and obesity, as well as response to beta-agonist therapy. These were evaluated in 726 individuals from 8 distinct ethnic populations (Chinese, Filipino, Southwest Asian, Saudi, Ghanaian, Kenyan, Sudanese, and European from Scotland). The results show that most haplotypes are shared among all populations, yet there are marked differences in their frequency distributions geographically. The genetic distance tree is different from standard human population distance trees, implying a different mode of evolution for this locus than that for human population gene-flow history. The multilocus frequency differences between the observed clusters of populations correspond to historical haplotype groupings that have been found to be functionally different with respect to multiple medically related phenotypes. Further studies are needed to see if functional relationships are the same across populations. 相似文献
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