RESUMO
Polymorphisms in interleukin genes (IL-6 and IL-10) are involved in the pathogenesis of breast cancer. This study investigated polymorphisms in the promoter regions of IL-6 (-174G/C) and IL-10 (-1082G/A) through a case-control study employing 80 female subjects who were pathologically diagnosed with breast cancer. All patients received follow-up care at the Mansoura University Hospital, Mansoura, Egypt. We included another 80 females (controls) from the same population, showing no signs of malignancy. Clinicopathological features were examined in the patient groups, including the expression of estrogen and progesterone receptors, involvement of the lymph node, tumor morphology, and tumor grades. Genotyping of the promoter polymorphisms was performed using allele-specific polymerase chain reaction method. There was a significant decrease in the mean age of menarche in the patient group than that in the normal individuals. For the IL-6 -174G/C polymorphism, there was a significantly higher frequency of the CC genotype in the patients than that in the controls (odds ratio = 5.49). Furthermore, the CC genotype was significantly more prevalent among the patients who had lymph node involvement. For the IL-10 -1082G/A polymorphism, there was no difference in the distribution of genotypes among the patients and the control subjects. However, the tumor size was significantly larger in patients who were harboring the AA genotype than that in the patients who had AG or GG genotypes.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Interleucina-10/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Egito , Feminino , Genótipo , Humanos , Menarca/genética , Regiões Promotoras Genéticas/genéticaRESUMO
An understanding of the ABO and Rh blood group systems is important for blood transfusions and is also pertinent due to their potential association with certain morbidities and susceptibilities to infections. To investigate the diversity and differentiation of the ABO and Rh loci in Middle Eastern populations, data from twelve representative Middle Eastern populations were analyzed. Six populations were in conformity with Hardy-Weinberg equilibrium at the ABO locus. The pooled heterozygosity at both loci was calculated to be highest in the sample from Jordan and lowest in Bahrain. Heterogeneity was pronounced in the Northern compared to the Southern Middle Eastern populations. Overall, the absolute gene diversity was 0.0046 and gene differentiation was calculated to be 0.0100. Genetic diversity of the studied loci across all populations (HT) was estimated to be 0.4594, while the diversity within the populations (HS) was 0.4548. Nei's genetic distance analyses revealed highest affinities between the populations of Kuwait and Qatar, Oman and Yemen, and between Qatar and the United Arab Emirates. These results were displayed through a UGPMA dendrogram and principal component analyses, which established clustering of certain populations. Clinal trends of the allelic systems were observed by generating contour maps that allow a detailed appreciation of the distributions of alleles across the geography of the Arabian Peninsula and the Middle East. Taken together, these analyses are helpful in understanding the differentiation of blood group loci and for designing prospective studies for establishing the associations of these loci with health variables in the populations studied.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Alelos , Árabes/genética , Loci Gênicos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Sistema ABO de Grupos Sanguíneos/classificação , Árabes/classificação , Análise por Conglomerados , Frequência do Gene , Ligação Genética , Variação Genética , Heterozigoto , Humanos , Oriente Médio , Filogenia , Filogeografia , Análise de Componente Principal , Sistema do Grupo Sanguíneo Rh-Hr/classificaçãoRESUMO
In order to investigate the diversity of ABO and Rh blood group genes in the Saudi Arabian population, we assembled the phenotypic data of approximately 66,000 subjects from ten representative Saudi populations: Al-Khobar, Riyadh, Tabuk/Madina Al-Munawaara, Jeddah, Abha, South region, Sakaka, Domah, Al-Qurayat, and Sweer. The frequencies of p[A], q[B], and r[O] alleles at the ABO locus were observed to be 0.1688, 0.1242, and 0.7070, respectively, and the frequency of the D allele at the Rh locus was 0.7138. The heterozygosities at the ABO and Rh loci were 0.4563 and 0.4086, respectively, while the combined heterozygosity was 0.4324. Homogeneity tests revealed the population of Abha to be the most heterogeneous while that of Tabuk/Madina was found to be the least heterogeneous. Homogeneity was higher among the Northern populations while Southern populations demonstrated subdivisions and stratification. Gene diversity analyses yielded a total heterozygosity value of 0.4449. The coefficient of gene differentiation was 0.0090. Nei's genetic distance analyses showed that there was close affinity between the populations of Al-Khobar and Riyadh. The largest differences were observed between the populations of Sakaka and Domah. Furthermore, negative correlations were found between p[A] and r[O] alleles, and between q[B] and r[O] alleles at the ABO locus. Clinal analyses revealed that the r[O] allele showed an increasing trend from North-East to South-West, and conversely the q[B] allele exhibited a decreasing trend at these coordinates. These analyses present interesting aspects of the blood group allele distribution across the geography of Saudi Arabia.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Heterogeneidade Genética , Variação Genética , Genética Populacional , Sistema do Grupo Sanguíneo Rh-Hr/genética , Alelos , Frequência do Gene/genética , Loci Gênicos , Geografia , Heterozigoto , Humanos , Fenótipo , Filogenia , Análise de Componente Principal , Arábia SauditaRESUMO
We investigated systolic dysfunction by the use of biochemical laboratory tests and perfusion single-photon emission computed tomography imaging in 32 Pakistani subjects exhibiting symptoms of this disorder. To investigate underlying genetic causes, such as familial hypercholesterolemia, DNA samples from these subjects were screened by PCR-SSCP and DNA sequencing to detect changes in the low density lipoprotein receptor gene (LDLR). A novel mutation (1171G>A) in exon 8 and two polymorphisms (1167G>A and 1413 A>G) in exons 8 and 10 of the LDLR gene were found. In silico tools such as SIFT, PolyPhen-2, KD4v, and Project HOPE were used to predict the effect of this mutation on protein structure and function.
Assuntos
Mutação de Sentido Incorreto , Receptores de LDL/genética , Disfunção Ventricular Esquerda/genética , Adolescente , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Éxons , Feminino , Estudos de Associação Genética , Humanos , Masculino , Modelos Moleculares , Polimorfismo de Nucleotídeo Único , Polimorfismo Conformacional de Fita Simples , Estrutura Terciária de Proteína , Receptores de LDL/química , Volume Sistólico , Sístole , Tomografia Computadorizada de Emissão de Fóton Único , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto JovemRESUMO
Infection of mothers with schistosomiasis and filariasis has been shown to influence infant responses to neonatal Bacille Calmette-Guérin (BCG) immunization. The genetic makeup of infants is also considered an important determinant for the activity of BCG vaccine. The effect of natural resistance-associated macrophage protein 1 (NRAMP1) gene polymorphism on the efficacy of BCG vaccine was examined in neonates with helminth-infected mothers (63 infants) and the results were compared with neonates of uninfected mothers (187 infants). After BCG vaccination, assessment of scar presence, tuberculin test, stool analysis, and IgE level was performed. Polymorphism of the NRAMP1 gene was investigated by PCR amplification followed by RFLP analysis. We found that patients with heterozygosity of intron 4 (GC) and/or maternal infection with helminth parasites showed reduced efficacy of BCG vaccine against tuberculosis.