FTHL17, PRM2, CABYR, CPXCR1, ADAM29, and CABS1 are highly expressed in colon cancer patients and are regulated in vitro by epigenetic alterations.

Background: Colon cancer is a serious public health issue and a major cause of cancer-related mortality worldwide, including Saudi Arabia. Knowledge of genes associated with colon cancer development and progression is essential for identifying new cancer-specific biomarkers to improve the diagnosis of colon cancer. Methods: The expression levels of FTHL17, PRM2, CABYR, CPXCR1, ADAM29, and CABS1 in 15 adjacent colon cancer and normal colon tissue samples from male patients were investigated using reverse transcription polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR) assays. qRT-PCR analysis was also used to determine whether reducing DNA methyltransferase (via 5-aza-2'-deoxycytidine treatment) or histone deacetylation (via trichostatin treatment) increased the expression levels of the tested genes. Results: The analysis of the 15 colon cancer and adjacent normal colon tissue samples revealed that all six genes were expressed in both groups, but their expression levels were significantly higher in the colon cancer group. Furthermore, the mRNA expression levels of the FTHL17, PRM2, CABYR, CPXCR1, and ADAM29 genes were considerably upregulated after treatment of HCT116 and Caco-2 cells with 5-aza-2'-deoxycytidine and trichostatin. However, the CABS1 gene was activated only with trichostatin treatment. Conclusions: The findings of this study suggest that FTHL17, PRM2, CABYR, CPXCR1, ADAM29, and CABS1 are suitable candidate biomarkers of colon cancer and their expressions are regulated by hypomethylation and hyperacetylation.

Magnetically controlled drug delivery and hyperthermia effects of core-shell Cu@Mn3O4 nanoparticles towards cancer cells in vitro.

Recent increase in the integration of nanotechnology and nanosciences to the biomedical sector fetches the human wellness through the development of sustainable treatment methodologies for cancerous tumors at all stages of their initiation and progression. This involves the development of multifunctional theranostic probes that effectively support for the early cancer diagnosis, avoiding non-target cell toxicity, controlled and customized anticancer drug release etc. Therefore, to advance the field of nanotechnology-based sustainable cancer treatment, we fabricated and tested the efficacy of anticancer drug-loaded magnetic hybrid nanoparticles (NPs) towards in vitro cell culture systems. The developed conjugate of NPs was incorporated with the functions of both controlled drug delivery and heat-releasing ability using Mn3O4 (manganese oxide) magnetic core with Cu shell encapsulated within trimethyl chitosan (TMC) biopolymer. On characterization, the Cu@Mn3O4-TMC NPs were confirmed to have an approximate size of 130 nm with full agglomeration (as observed by the HRTEM) and crystal size of 92.95 ± 18.38 nm with tetragonal hausmannite phase for Mn3O4 spinel structure (XRD). Also, the UV-Vis and FTIR analysis provided the qualitative and quantitative effects of 5-fluororacil (5-Fu) anticancer drug loading (max 68 %) onto the Cu@Mn3O4-TMC NPs. The DLS analysis indicated for the occurrence of no significant changes to the particle size (around 100 nm) of Cu@Mn3O4-TMC due to the solution dispersion thereby confirming for the aqueous stability of developed NPs. In addition, the magnetization values of Cu@Mn3O4-TMC NPs were measured to be 34 emu/g and a blocking temperature of 42 K. Further tests of magnetic hyperthermia by the Cu@Mn3O4-TMC/5-Fu NPs provided that the heat-releasing capacity (% ΔT at 15 min) increases with that of increased frequency, i.e. 28 % (440 Hz) > 22.6 % (240 Hz) > 18 % (44 Hz), and the highest specific power loss (SPL) value observed to be 488 W/g for water. Moreover, the 5-Fu drug release studies indicate that the release is high at a pH of 5.2 and almost all the loaded drug is getting delivered under the influence of the external magnetic field (430 Hz) due to the influence of both Brownian-rotation and Néel relaxation heat-mediated mechanism. The pharmacokinetic drug release studies have suggested for the occurrence of more than one model, i.e. First-order, Higuchi (diffusion), and Korsemeyer-Peppas (non-Fickian), in addition to hyperthermia. Finally, the in vitro cell culture systems (MCF-7 cancer and MCF-10 non-cancer) helped to differentiate the physiological changes due to the effects of hyperthermia and 5-Fu drug individually and as a combination of both. The observed differences of cell viability losses among both cell types are measured and discussed with the expression of heat shock proteins (HSPs) by the MCF-10 cells as against the MCF-7 cancer cells. We believe that the results generated in this project can be helpful for the designing of new cancer therapeutic models with nominal adverse effects on healthy normal cells and thus paving a way for the treatment of cancer and other deadly diseases in a sustainable manner.

Genetic Variants of HOTAIR Associated with Colorectal Cancer: A Case-Control Study in the Saudi Population.

Genetic polymorphism in long noncoding RNA (lncRNA) HOTAIR is linked with the risk and susceptibility of various cancers in humans. The mechanism involved in the development of CRC is not fully understood but single nucleotide polymorphisms (SNPs) can be used to predict its risk and prognosis. In the present case-control study, we investigated the relationship between HOTAIR (rs12826786, rs920778, and rs1899663) polymorphisms and CRC risk in the Saudi population by genotyping using a TaqMan genotyping assay in 144 CRC cases and 144 age- and sex-matched controls. We found a significant (p < 0.05) association between SNP rs920778 G > A and CRC risk, and a protective role of SNPs rs12826786 (C > T) and rs1899663 (C > A) was noticed. The homozygous mutant "AA" genotype at rs920778 (G > A) showed a significant correlation with the female sex and colon tumor site. The homozygous TT in SNP rs12816786 (C > T) showed a significant protective association in the male and homozygous AA of SNP rs1899663 (C > A) with colon tumor site. These results indicate that HOTAIR can be a powerful biomarker for predicting the risk of colorectal cancer in the Saudi population. The association between HOTAIR gene polymorphisms and the risk of CRC in the Saudi population was reported for the first time here.

Green Synthesis of Silver Nanoparticles Using Aerial Part Extract of the Anthemis pseudocotula Boiss. Plant and Their Biological Activity.

Green syntheses of metallic nanoparticles using plant extracts as effective sources of reductants and stabilizers have attracted decent popularity due to their non-toxicity, environmental friendliness and rapid nature. The current study demonstrates the ecofriendly, facile and inexpensive synthesis of silver nanoparticles (AP-AgNPs) using the extract of aerial parts of the Anthemis pseudocotula Boiss. plant (AP). Herein, the aerial parts extract of AP performed a twin role of a reducing as well as a stabilizing agent. The green synthesized AP-AgNPs were characterized by several techniques such as XRD, UV-Vis, FT-IR, TEM, SEM and EDX. Furthermore, the antimicrobial and antibiofilm activity of as-prepared AP-AgNPs were examined by a standard two-fold microbroth dilution method and tissue culture plate methods, respectively, against several Gram-negative and Gram-positive bacterial strains and fungal species such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and Acinetobacter baumannii (MDR-AB), methicillin-resistant S. aureus (MRSA) and Candida albicans (C. albicans) strains. The antimicrobial activity results clearly indicated that the Gram-negative bacteria MDR-PA was most affected by AgNPs as compared to other Gram-negative and Gram-positive bacteria and fungi C. albicans. Whereas, in the case of antibiofilm activity, it has been found that AgNPs at 0.039 mg/mL, inhibit biofilms formation of Gram-negative bacteria i.e., MDR-PA, E. coli, and MDR-AB by 78.98 ± 1.12, 65.77 ± 1.05 and 66.94 ± 1.35%, respectively. On the other hand, at the same dose (i.e., 0.039 mg/mL), AP-AgNPs inhibits biofilm formation of Gram-positive bacteria i.e., MRSA, S. aureus and fungi C. albicans by 67.81 ± 0.99, 54.61 ± 1.11 and 56.22 ± 1.06%, respectively. The present work indicates the efficiency of green synthesized AP-AgNPs as good antimicrobial and antibiofilm agents against selected bacterial and fungal species.

Mn3O4 nanoparticles: Synthesis, characterization and their antimicrobial and anticancer activity against A549 and MCF-7 cell lines.

Due to their inexpensive and eco-friendly nature, and existence of manganese in various oxidation states and their natural abundance have attained significant attention for the formation of Mn3O4 nanoparticles (Mn3O4 NPs). Herein, we report the preparation of Mn3O4 nanoparticles using manganese nitrate as a precursor material by utilization of a precipitation technique. The as-prepared Mn3O4 nanoparticles (Mn3O4 NPs) were characterized by using X-ray powder diffraction (XRD), UV-Visible spectroscopy (UV-Vis), High-Resolution Transmission electron microscopy (HRTEM), Field emission scanning electron microscopy (FESEM), Thermal gravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR). The antimicrobial properties of the as-synthesized Mn3O4 nanoparticles were investigated against numerous bacterial and fungal strains including S. aureus, E. coli, B. subtilis, P. aeruginosa, A. flavus and C. albicans. The Mn3O4 NPs inhibited the growth of S. aureus with a minimum inhibitory concentration (MIC) of 40 µg/ml and C. albicans with a MIC of 15 µg/ml. Furthermore, the Mn3O4 NPs anti-cancer activity was examined using MTT essay against A549 lung and MCF-7 breast cancer cell lines. The Mn3O4 NPs revealed significant activity against the examined cancer cell lines A549 and MCF-7. The IC50 values of Mn3O4 NPs with A549 cell line was found at concentration of 98 µg/mL and MCF-7 cell line was found at concentration of 25 µg/mL.

A novel biocompatible formate bridged 1D-Cu(ii) coordination polymer induces apoptosis selectively in human lung adenocarcinoma (A549) cells.

Copper compounds are promising candidates for next-generation metal anticancer drugs. Therefore, we synthesized and characterized a formate bridged 1D coordination polymer [Cu(L)(HCOO)2]n, (L = 2-methoxy-6-methyl-3-((quinolin-8-ylimino)methyl)chroman-4-ol), PCU1, wherein the Cu(ii) center adopts a square pyramidal coordination environment with adjacent CuCu distances of 5.28 Å. Primarily, in vitro DNA interaction studies revealed a metallopolymer which possesses high DNA binding propensity and cleaves DNA via the oxidative pathway. We further analysed its potential on cancerous cells MCF-7, HeLa, A549, and two non-tumorigenic cells HEK293 and HBE. The selective cytotoxicity potential of PCU1 against A549 cells driven us to examine the mechanistic pathways comprehensively by carrying out various assays viz, cell cycle arrest, Annexin V-FTIC/PI assay, autophagy, intercellular localization, mitochondrial membrane potential 'MMP', antiproliferative assay, and gene expression of TGF-ß and MMP-2.

Two novel SNPs in genes involved in immune response and their association with mandibular residual ridge resorption.

"Residual ridge resorption" (RRR) is a multifactorial condition involving bone resorption of the residual ridge. We investigated 10 single nucleotide polymorphisms (SNPs) in seven genes with the aim of identifying the genetic factors associated with RRR susceptibility. The study group included 96 RRR patients and 96 controls. Age at first edentulism, duration of edentulism, and bone height were recorded. Saliva was collected from the subjects for DNA extraction. Genotype analysis was performed on the 'SequenomMassARRAYiPLEX'. The genotype and allele frequencies calculated in patients and controls were compared. We found that rs1800896 in the IL10 gene and rs5743289 in NOD2 gene showed significant association with RRR. Within the RRR group, genotypes for each SNP were separated, and we observed that the age at first edentulism and bone height showed variations in the different genotypes of the ten studied SNPs. This study showed an association between SNPs in IL10 and NOD2 genes. It also revealed that the genotypes of the different SNPs influence bone resorption and health. Additionally, age at first edentulism and bone height were much lower in some genotypes. This study demonstrates the need for larger multicenter trials to confirm these findings. Finally, we suggest that the results of this study may be utilized for developing novel genetic diagnostic tests and for identifying Saudi individuals who may be more susceptible to RRR development following dental extraction.

Toll-like receptor 4 polymorphisms in Saudi population with cardiovascular diseases.

BACKGROUND: Toll-like receptors play a substantial role in innate immunity and the effects of TLR4 genetic variants on cardiovascular diseases are still largely unknown. Therefore, we aimed to investigate the effects of TLR4 polymorphisms on cardiovascular diseases risk in the Saudi population. METHODS: Three tag single-nucleotide polymorphisms (rs2770150, rs10759931, and rs4986790) in TLR4 were studied on 222 unrelated patients with cardiovascular diseases and 190 healthy volunteers. RESULTS: We found that, in patients over 60 years old, the frequency of the TT genotype in rs2770150 and the variant allele G in rs10759931 were higher compared to the control group. Based on gender, the genotype frequency of rs2770150 increases the risk for cardiovascular diseases in female patients by 3.6-fold. The allele frequency for the G allele of rs10759931 increased the risk for CVDs in male patients by more than 1.5-fold. Furthermore, the genotype frequency of rs2770150 had a significant association with cardiovascular diseases in patients without hypertension and G allele of rs10759931 significantly increased the risk of cardiovascular diseases in patients that smoked. After Bonferroni correction only patients without hypertension showed significant risk of CVD with rs2770150. CONCLUSION: A deeper understanding of the genetic variability of TLR4 will enable us to better identification of biomarkers for early detection and prognosis, and also enhance the decision-making process of treatments for cardiovascular diseases.

No genetic relationship between TLR2 rs4696480, rs3804100, and rs3804099 gene polymorphisms and female breast cancer in Saudi populations.

Breast cancer (BC) is the most common cause of cancer-related deaths among women in the Kingdom of Saudi Arabia. An association between the dysregulation of innate immunity, primarily the deregulation of Toll-like receptors (TLRs), and BC development was described a long time ago. Several studies have reported that BC risk factors appear to be related to the interaction between certain genes and exposure to various environmental factors. Here, we investigated the potential correlation of three TLR2 single-nucleotide polymorphisms (SNPs; rs3804100, rs4696480, and rs3804099) with the development of BC in female patients from Saudi Arabia. We collected 126 blood samples from women with BC and 146 blood samples from healthy women without any clinical signs of BC. The genotypic frequencies of TLR2 polymorphisms were assayed. Our results showed that the genotypic and allelic frequencies of TLR2 did not differ significantly between BC patients and healthy controls. However, the distributions of rs3804100 (1350 T/C) genotypes in BC groups were 1%, 19%, and 80% for CC, CT, and TT, respectively. In the control group, the rs3804100 (1350 T/C) genotype distributions were 3%, 18%, and 79% for CC, CT, and TT, respectively. The SNP rs3804100 homozygous "TT" genotype was not associated with the risk of developing BC in the BC patients compared with controls (odds ratio [OR], 4.5; confidence interval [CI], 0.49-41.02; P=0.145). The TLR2 rs4696480 AA genotype was observed in 23% of BC patients compared to 18% of control individuals, the AT genotype was seen in 40% of BC patients and 46% of control individuals, and the TT genotype was observed in 37% of BC patients and 36% of normal controls. Our results did not show any difference in genotypic frequency between BC patients and normal controls for the TLR2 rs3804099 SNP; however, the (C) phenotypic frequency was 49% in BC patients and 53% in controls. The (T) phenotypic frequency was 51% and 47% in BC patients and normal patients, respectively. These findings indicate that there is no association between the TLR2 polymorphisms tested and BC susceptibility in the female population from the Kingdom of Saudi Arabia. We suggest using other TLR2 SNPs to investigate the possible relationship between innate immunity deregulation by disruption of TLR2 and potential BC development.

Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients.

OBJECTIVE: The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. METHODS: In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene's promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. RESULTS: The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. CONCLUSION: The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer.

The hOGG1 Ser326Cys Gene Polymorphism and Breast Cancer Risk in Saudi Population.

The purpose of this study was to test the association between human 8-oxoguanine glycosylase 1 (hOGG1) gene polymorphisms and susceptibility to breast cancer in Saudi population. We have also aimed to screen the hOGG1 Ser326Cys polymorphism effect on structural and functional properties of the hOGG1 protein using in silico tools. We have analyzed four SNPs of hOGG1 gene among Saudi breast cancer patients along with healthy controls. Genotypes were screened using TaqMan SNP genotype analysis method. Experimental data was analyzed using Chi-square, t test and logistic regression analysis using SPSS software (v.16). In silco analysis was conducted using discovery studio and HOPE program. Genotypic analysis showed that hOGG1 rs1052133 (Ser326Cys) is significantly associated with breast cancer samples in Saudi population, however rs293795 (T >C), rs2072668 (C>G) and rs2075747 (G >A) did not show any association with breast cancer. The hOGG1 SNP rs1052133 (Ser326Cys) minor allele T showed a significant association with breast cancer samples (OR = 1.78, χ2 = 7.86, p = 0.02024). In silico structural analysis was carried out to compare the wild type (Ser326) and mutant (Cys326) protein structures. The structural prediction studies revealed that Ser326Cys variant may destabilize the protein structure and it may disturb the hOGG1 function. Taken together this is the first In silico study report to confirm Ser326Cys variant effect on structural and functional properties of hOGG1 gene and Ser326Cys role in breast cancer susceptibility in Saudi population.

Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-κB Mediated Inflammation in Colon Cancer Patients.

Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-κB pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infections by bacteria in the human colon and leads to induction of an acute secretion of inflammatory cytokines mediated by NF-κB. Also, we report here a clear evidence for an association between TLR4 rs10759931 polymorphism (OR = 0.086, CI: 0.04-0.18, P = <0.00001). This polymorphism affects the entire population without being specific to either gender or to any age group. In contrast, the rs2770150 is associated with colon cancer in women aged over 50 years and is closely linked with the decreased levels of female sex hormones during the post-menopausal period (OR = 0.188, CI: 0.074-0.48, P = <0.00084). rs10759932 and rs4986790 appear to have any association with colon cancer. Our data suggest that TLR4 SNPs could possibly serve as biomarkers for decision making in colon cancer treatment.

No associations between aromatase gene polymorphisms and breast cancer risk in Saudi patients.

BACKGROUND: Cytochrome P450 (CYP)19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among women with breast cancer. The aim of this study was to analyze the genetic association of rs4646 (A > C) and rs700518 (Val > Val) in the CYP19A1 gene with the risk of breast cancer. METHODS: These two single nucleotide polymorphisms (SNPs) were analyzed in a primary study group of breast cancer patients and healthy control subjects. Genotypes were determined by the TaqMan SNP analysis technique. The study data were analyzed using the chi-square or t-test and logistic regression analysis by Statistical Package for the Social Sciences version 16 software. RESULTS: rs4646 and rs700518 had no association with susceptibility to breast cancer. There was no significant association for either of these SNPs overall in breast cancer samples when compared with healthy control samples. Our data do not support a relationship between the CYP19A1 rs4646 and rs700518 SNPs and risk of breast cancer. It may be that there are ethnic differences with regard to this relationship. CONCLUSION: This study demonstrated that CYP19A1 rs4646 and rs700518 SNPs may not be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of other ethnicities could provide evidence for the role of the CYP19A1 gene in breast carcinomas.

Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk.

OBJECTIVE: The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population. METHODS: We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation. RESULTS: Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk. CONCLUSION: Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population.

Development and characterisation of nine polymorphic microsatellite markers for Tephrosia calophylla Bedd. (Fabaceae).

Tephrosia calophylla Bedd. (Fabaceae) is an endangered tropical plant endemic to southwestern Ghats, India. The objective of this study was to contribute to the characterisation of the diversity of this rare species, which is necessary for its future conservation. Accordingly, microsatellite markers were designed, and their ability to detect polymorphisms was determined. Nine microsatellite markers were developed using genomic libraries, and all of the markers were successfully amplified in 42 individuals. Three to nine alleles per locus were observed, and the heterozygosity of the loci ranged from 0.381 to 0.905. The nine newly developed polymorphic markers recognise a sufficient number of varying loci to perform further studies on the conservation and breeding of this medicinal cultivar.

Novel mutations in IL-10 promoter region -377 (C>T), -150 (C>A) and their association with psoriasis in the saudi population.

BACKGROUND: Psoriasis, a common cutaneous disorder characterized by inflammation and abnormal epidermal proliferation with a prevalence of 2-3% in the general population, may be linked to certain types of cancer. Several studies have reported an association between interleukin 10 (IL-10) variant polymorphisms and inflammatory diseases such as psoriasis vulgaris although the results vary according to the population studied. No studies have been performed in the Saudi population. The present study concerned novel variants and other genetic polymorphisms of the promoter and exonic regions of the IL10 gene in patients with moderate to severe psoriasis and potential differences in genotype compared to a group of healthy volunteers. MATERIALS AND METHODS: Patients with moderate to severe psoriasis and healthy controls with no personal or family history of psoriasis were selected from the central region of Saudi Arabia. Polymorphisms of the IL 10 gene of both groups were genotyped. RESULTS: We observed two novel variants in 5'UTR region of the promoter precursor with higher prevalence of the genotype with both wild-type alleles in patients compared to the healthy control group. The differences at positions -377 and -150 were significantly associated with disease, both the variants conferred strong protection against psoriasis in Saudi patients. CONCLUSIONS: This observation provides further support for the importance of the part that IL10 plays in the pathophysiology of this disease. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of IL-10 in psoriasis.

DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia.

DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population.

Modeling and analysis of soybean (Glycine max. L) Cu/Zn, Mn and Fe superoxide dismutases.

Superoxide dismutase (SOD, EC 1.15.1.1) is an important metal-containing antioxidant enzyme that provides the first line of defense against toxic superoxide radicals by catalyzing their dismutation to oxygen and hydrogen peroxide. SOD is classified into four metalloprotein isoforms, namely, Cu/Zn SOD, Mn SOD, Ni SOD and Fe SOD. The structural models of soybean SOD isoforms have not yet been solved. In this study, we describe structural models for soybean Cu/Zn SOD, Mn SOD and Fe SOD and provide insights into the molecular function of this metal-binding enzyme in improving tolerance to oxidative stress in plants.

The C allele of a synonymous SNP (rs1805414, Ala284Ala) in PARP1 is a risk factor for susceptibility to breast cancer in Saudi patients.

BACKGROUND: Genetic aberrations of DNA repair enzymes are known to be common events associated with different cancer entities. The aim of the present study was to analyze genetic associations of rs1805404 (Asp81Asp) and rs1805414 (Ala284Ala) in the PARP1 gene with the risk of breast cancer in Saudi Arabia. MATERIALS AND METHODS: These two SNP's were analyzed in a primary study group of breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP testing and analyzed using Chi-square or t test and logistic regression analysis with SPSS16.0 software. RESULTS AND CONCLUSIONS: Results showed that rs1805414 was associated with a significantly increased susceptibility to breast cancer, significant risk being observed for the TC, CC and TC+CC genotypes. In conclusion PARP1 rs1805414 SNP polymorphisms may be involved in the etiology of breast cancer in the Saudi population. In contrast, PARP1 rs1805404 did not show any significant association in overall in breast cancer samples when compared to healthy controls. Confirmation of our findings in larger populations of different ethnicities may provide evidence for a role of the PARP1 gene in breast carcinoma developnment.

Association between PARP-1 V762A polymorphism and breast cancer susceptibility in Saudi population.

Genetic aberrations of DNA repair enzymes are known to be common events and to be associated with different cancer entities. Aim of the following study was to analyze the genetic association of rs1136410 (Val762Ala) in PARP1 gene with the risk of breast cancer using genotypic assays and insilico structural predictions. Genotypic analysis of individual locus showed statistically significant association of Val762Ala with increased susceptibility to breast cancer. Protein structural analysis was performed with Val762Ala variant allele and compared with the predicted native protein structure. Protein prediction analysis showed that this nsSNP may cause changes in the protein structure and it is associated with the disease. In addition to the native and mutant 3D structures of PARP1 were also analyzed using solvent accessibility models for further protein stability confirmation. Taken together, this the first study that confirmed Val762Ala variant has functional effect and structural impact on the PARP1 and may play an important role in breast cancer progression in Saudi population.