Potential Impact of Vascular Endothelial Growth Factor Gene Variation (-2578C>A) on Breast Cancer Susceptibility in Saudi Arabia: a Case-Control Study
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ABSTRACT:
SUBMITTER: Al Balawi IA
PROVIDER: S-EPMC6031782 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
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Potential Impact of Vascular Endothelial Growth Factor Gene Variation (-2578C>A) on Breast Cancer Susceptibility in Saudi Arabia: a Case-Control Study
Al Balawi Ibrahim Abdullah IA Mir Rashid R Abu-Duhier F M FM
Asian Pacific journal of cancer prevention : APJCP 20180427 4
Aim: VEGF gene polymorphisms can induce either increase or inhibition of VEGF secretion, with altered promoter activity. The VEGF rs699947 SNP is located in the promoter region and is associated with susceptibility to breast carcinoma development. Here, we investigated the association of the -2578C>A polymorphism in the VEGF gene with breast cancer risk in Saudi women. Methodology: Genotyping of the VEGF-gene variation (-2578A>C) was performed using the amplification refractory mutation system P ...[more]
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Project description:Background and objectiveVascular endothelial growth factor (VEGF) is one of the key initiators and regulators of angiogenesis and it plays a vital role in the onset and development of malignancy. The association between VEGF gene polymorphisms and lung cancer risk has been extensively studied in recent years, but currently available results remain controversial or ambiguous. The aim of this meta-analysis is to investigate the associations between four common VEGF polymorphisms (i.e., -2578C>A, -460C>T, +936C>T and +405C>G) and lung cancer risk.MethodsA comprehensive search was conducted to identify all eligible studies to estimate the association between VEGF polymorphisms and lung cancer risk. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of this association.ResultsA total of 14 published case-control studies with 4,664 cases and 4,571 control subjects were identified. Our meta-analysis provides strong evidence that VEGF -2578C>A polymorphism is capable of increasing lung cancer susceptibility, especially among smokers and lung squamous cell carcinoma (SCC) patients. Additionally, for +936C>T polymorphism, increased lung cancer susceptibility was only observed among lung adenocarcinoma patients. In contrast, VEGF -460C>T polymorphism may be a protective factor among nonsmokers and SCC patients. Nevertheless, we did not find any association between +405C>G polymorphism and lung cancer risk, even when the groups were stratified by ethnicity, smoking status or histological type.ConclusionThis meta-analysis recommends more investigations into the relationship between -2578C>A and -460C>T lung cancer risks. More detailed and well-designed studies should be conducted to identify the causal variants and the underlying mechanisms of the possible associations.
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Project description:Morphological abnormalities in hippocampus have been implicated in neuropsychiatric disorders, including depression, schizophrenia, and dementia. Vascular endothelial growth factor (VEGF) has been demonstrated to have neurogenic effects in the hippocampus in rats. However, influence of VEGF variation on hippocampus morphology in humans has yet to be shown. Here, an integrated genetic and neuroimaging approach was used to investigate whether VEGF variation influences hippocampus morphology in humans.High-resolution magnetic resonance imaging and voxel-based morphometry were used to identify the influence of genetic variation of VEGFA [rs833068 (SNP-1), rs833070 (SNP-2), rs2146323 (SNP-3) and rs3025020 (SNP-4)] on brain morphology in 47 healthy individuals.Variation in VEGFA SNP-2 and SNP-3 showed significant effects on hippocampus concentration.The findings suggest that effects of VEGF in hippocampus found in rats extend to humans; further understanding of effects of VEGFA variation might have important implications in identifying individuals more vulnerable to hippocampus pathology as well as those neuropsychiatric populations most likely to benefit from VEGF-mediated interventions.
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Project description:BackgroundDiabetic retinopathy (DR) is one of the complications in diabetes mellitus (DM) which caused by microvascular-damage in the retina due to long termmetabolic changes in diabetes. To date, there has been much research targeted on the determinant of genetic identification in DR patients. In DR, Vascular Endothelial Growth Factor (VEGF) gene is accountable for breaking down the blood-retinal barrier and implicated in the role of neovascularization. It is thought that the polymorphism of VEGF -2578C/A (rs699947) contributed to the development of diabetic retinopathy in type 2 DM.AimTo determine whether the polymorphisms of VEGF-2578C/A are the risk factors for DR in type 2 DM patients in Bali, Indonesia.MethodsThis study is a case-control model comparing 33 cases DR patients in type-2 diabetes mellitus and 35 cases of non-DR as controls in Balinese ethnic. Polymorphisms of VEGF-2578C/A were examined by PCR analysis and DNA sequencing on rs699947 to identify any variation in A/C/T allele distribution. Chi-square test was used to analyze the data and determine the relation of polymorphism and DR.ResultsThis research showed the genetic variation existence in VEGF-2578C/A polymorphism significantly (p = 0,000) with C allele was higher in the DR group, in contrast, A and T allele were greater in the non-DR group compared to DR group. The result showed that C allele in VEGF-2578 contributed as a risk factor (OR = 13.05; 95% CI = 2.69-63.18; p = 0.001) for DR in type-2 DM (T2DM) patients in Bali, Indonesia.ConclusionPolymorphism of VEGF-2578C/A (rs699947) allele distribution can be concluded as a risk factor of DR within T2DM patients in Bali, Indonesia. This study may also be used to expand the knowledge in managing DR patients at an earlier stage to avoid further complications.
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Project description:BackgroundCystinuria is an inherited metabolic disease that is caused by defects in two genes, SLC3A1 and SLC7A9, which result in a renal reabsorptive defect of cystine and other dibasic amino acids, including ornithine, arginine, and lysine. Patients usually present with recurrent renal calculi and may develop renal impairment. Medical management includes high fluid intake and chelating agents. To the best of our knowledge, this is the first study describing cystinuria in Saudi Arabia.MethodsA retrospective chart review for cystinuria patients from the genetic and nephrology divisions between 2010 to 2015. All patients were investigated, diagnosed and treated at King Abdulaziz Medical City in Saudi Arabia.ResultsEight patients were identified from five unrelated families. The age of onset ranged from birth to 14 years. The female to male ratio was 1.7:1. Two new variants in the SLC3A1 and SLC9A7 genes were discovered. All of the detected mutations were missense variants in three different exons, such as c.1711 T > A (p.Cys571Ser) (exon 10), c.1166C > T p.Thr389Met (exon 11) and c.1400 T > A p.Met467Lys (exon 8). Additionally, 37.5% of our patients developed arterial hypertension and 25% had urinary tract infection, but none had renal impairment. No significant clinical differences were detected in this study between type A (SLC3A1 variants) and type B cystinuria (SLC7A9 variant). Two cases were diagnosed based on clinical information, biochemical testing and a positive family history as all of the molecular testing for cystinuria was negative.ConclusionCystinuria has wide genetic heterogeneity with a poor genotype/phenotype correlation. Negative molecular investigations should not rule out the disease if clinical and biochemical investigations support the diagnosis. A larger data registry is essential to better describe the cystinuria genotype/phenotype in Saudi Arabia.
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