• Genomics & Informatics
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• 제10권2호
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• pp.99-105
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• 2012

Dyslipidemia, mainly characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, is an important etiological factor in the development of cardiovascular disease (CVD). Considering the relationship between childhood obesity and CVD risk, it would be worthwhile to evaluate whether previously identified lipid-related variants in adult subjects are associated with lipid variations in a childhood obesity study (n = 482). In an association analysis for 16 genome-wide association study (GWAS)-based candidate loci, we confirmed significant associations of a genetic predisposition to lipoprotein concentrations in a childhood obesity study. Having two loci (rs10503669 at LPL and rs16940212 at LIPC) that showed the strongest association with blood levels of TG and HDL-C, we calculated a genetic risk score (GRS), representing the sum of the risk alleles. It has been observed that increasing GRS is significantly associated with decreased HDL-C (effect size, $-1.13{\pm}0.07$) compared to single nucleotide polymorphism combinations without two risk variants. In addition, a positive correlation was observed between allelic dosage score and risk allele (rs10503669 at LPL) on high TG levels (effect size, $10.89{\pm}0.84$). These two loci yielded consistent associations in our previous meta-analysis. Taken together, our findings demonstrate that the genetic architecture of circulating lipid levels (TG and HDL-C) overlap to a large extent in childhood as well as in adulthood. Post-GWAS functional characterization of these variants is further required to elucidate their pathophysiological roles and biological mechanisms.

• BMB Reports
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• 제43권10호
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• pp.693-697
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• 2010

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome characterized by predisposition to early-onset cancers. HNPCC is caused by heterozygous loss-of-function mutations within the mismatch repair genes MLH1, MSH2, MSH6, PMS1, and PMS2. We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery. Five Lynch syndrome patients carried germline mutations in MLH1 or MSH2. Two of these were identified as known mutations in MLH1: deletion of exon 10 and a point mutation (V384D). The remaining three patients exhibited novel mutations: a duplication (937_942dupGAAGTT) in MLH1; deletion of exons 8, 9, and 10; and a point mutation in MLH1 (F396I) combined with multiple missense mutations in MSH2 (D295G, K808E, Q855P, and I884T). The findings underline the importance of efficient pre-screening of conspicuous cases.

• Clinical and Experimental Pediatrics
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• 제57권11호
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• pp.472-478
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• 2014

Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7091-7094
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• 2013

DNA repair capacity is crucial in maintaining cellular functions and homeostasis. However, it can be altered based on DNA sequence variations in DNA repair genes and this may lead to the development of many diseases including malignancies. Identification of genetic polymorphisms responsible for reduced DNA repair capacity is necessary for better prevention. Homologous recombination (HR), a major double strand break repair pathway, plays a critical role in maintaining the genome stability. The present study was performed to determine the frequency of the HR gene XRCC3 Exon 7 (C18067T, rs861539) polymorphisms in Saudi Arabian population in comparison with epidemiological studies by "MEDLINE" search to equate with global populations. The variant allelic (T) frequency of XRCC3 (C>T) was found to be 39%. Our results suggest that frequency of XRCC3 (C>T) DNA repair gene exhibits distinctive patterns compared with the Saudi Arabian population and this might be attributed to ethnic variation. The present findings may help in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.

• Environmental Engineering Research
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• 제21권2호
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• pp.109-120
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• 2016

Conventional treatment techniques cannot meet the stringent modern water quality regulations emanating from the need to provide high quality drinking water. Therefore, a number of studies have suggested low pressure membrane filtration as a worthwhile alternative. However, a major constraint to the extensive use of this technology in low and middle income countries is the high operating and maintenance costs caused by the inherent predisposition to membrane fouling. Notwithstanding, pretreatment of feed water using techniques such as coagulation, adsorption, oxidation and bio-filtration is believed to control fouling. In this review paper, the existing scientific knowledge on membrane fouling and pretreatment techniques for controlling fouling in low pressure membranes is analyzed with the aim of providing new and valuable insights into such techniques, as well as unveiling crucial issues noteworthy for further studies. Among the techniques reviewed, coagulation was observed to be the most cost-effective and will remain the most dominant in the coming years. Although oxidants and magnetic ion exchange resins can also control fouling, the propensity of oxidants to form health treating precursors and the high economic implications of magnetic ion exchange resins will hinder their adoption in developing countries.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.553-556
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• 2013

Background: This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years. Materials and Methods: A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features. Results: The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer. Conclusions: There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3959-3962
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• 2016

The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our ndings indicated that promoter methylation of TET2 signi cantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was signi cantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to con rm our ndings.

• Genomics & Informatics
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• 제10권4호
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• pp.239-243
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• 2012

Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy that is suspected to have a strong genetic predisposition. It is associated with poor perinatal outcome, and both GDM women and their offspring are at increased risk of future development of type 2 diabetes mellitus (T2DM). During the past several years, there has been progress in finding the genetic risk factors of GDM in relation to T2DM. Some of the genetic variants that were proven to be significantly associated with T2DM are also genetic risk factors of GDM. Recently, a genome-wide association study of GDM was performed and reported that genetic variants in CDKAL1 and MTNR1B were associated with GDM at a genome-wide significance level. Current investigations using next-generation sequencing will improve our insight into the pathophysiology of GDM. It would be important to know whether genetic information revealed from these studies could improve our prediction of GDM and the future development of T2DM. We hope further research on the genetics of GDM would ultimately lead us to personalized genomic medicine and improved patient care.

• Genomics & Informatics
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• 제11권1호
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• pp.34-37
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• 2013

This study evaluated the effects of somatic mutations and single nucleotide polymorphisms (SNPs) on disease progression and tried to verify the two-hit theory in cancer pathogenesis. To address this issue, SNP analysis was performed using the UCSC hg19 program in 10 acute myeloid leukemia patients (samples, G1 to G10), and somatic mutations were identified in the same tumor sample using SomaticSniper and VarScan2. SNPs in KRAS were detected in 4 out of 10 different individuals, and those of DNMT3A were detected in 5 of the same patient cohort. In 2 patients, both KRAS and DNMT3A were detected simultaneously. A somatic mutation in IDH2 was detected in these 2 patients. One of the patients had an additional mutation in FLT3, while the other patient had an NPM1 mutation. The patient with an FLT3 mutation relapsed shortly after attaining remission, while the other patient with the NPM1 mutation did not suffer a relapse. Our results indicate that SNPs with additional somatic mutations affect the prognosis of AML.

• Journal of Genetic Medicine
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• 제11권1호
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• pp.1-10
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• 2014

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic ${\beta}$-cells resulting in insulin deficiency. The genetic determinants of T1D susceptibility have been linked to several loci, in particular to the human leukocyte antigen (HLA) region, which accounts for 50% of the genetic risk of developing T1D. Multiple genes in the HLA region, which are in strong linkage disequilibrium, are thought to be involved. Another important locus, with a smaller effect on genetic predisposition to T1D, is the insulin gene. The advent of numerous single nucleotide polymorphism markers and genome screening has enabled the identification of dozens of new T1D susceptibility loci. Some of them appear to predispose to T1D independently of the HLA and may be important in families with T1D who lack strong HLA susceptibility. Other loci may interact with each other to cause susceptibility. The autoimmune response against ${\beta}$-cells can also be triggered by environmental factors in the presence of a predisposing genetic background. Deciphering the environmental and genetic factors involved should help to understand the origin of T1D and aid in the design of individualized prevention programs.