Genetic Polymorphism of Angiotensin II Type 1 Receptors and Their Effect on the Clinical Outcome of Captopril Treatment in Arab Iraqi Patients with Acute Coronary Syndrome (Mid Euphrates)

Genetic variation in the angiotensin II type 1 receptor (AT1R) has an important effect on the outcome of acute coronary syndrome (ACS) initiated treatment with captopril. This study aims to investigate the impact of genetic polymorphism of AT1R (rs5186 and rs275651) on the ACS outcome in Iraqi patients treated with captopril. A total of 250 Iraqi individuals with ACS were included in this case—control study and they were divided into two study groups; Study group 1 included 125 participants who were prescribed captopril, 25 mg twice daily and study group 2 included 125 participants who received no captopril as part of their ACS treatment (control study). The AT1R gene (rs5186) CC genotype was found to be associated with ST-elevation myocardial infarction (STEMI) (Odd’s ratio (O.R) = 1.2, P = 0.7), while AC was associated with Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) (O.R = 1.2, P = 0.8). AC genotype is more prone to have Percutaneous coronary intervention (PCI) after ACS attack (O.R = 1.2, P = 0.6). CC genotype had a risk to get less improvement (O.R = 1.6, P = 0.5), so might require higher doses of captopril during acute coronary insult. The AT1R gene (rs275651) AA genotype was associated with UA (O.R = 1.3, P = 0.9). AA and AT genotypes were more prone to have PCI after ACS attack (O.R = 3.9 P = 0.2, O.R = 3.5, P = 0.3 respectively) and thus requiring higher doses of captopril. We conclude that the AT1R rs5186, rs275651 genetic polymorphisms might partially affect the clinical outcome of ACS patients treated with captopril and might have captopril resistance which requires higher doses.     

Solution pH change in non-uniform alternating current electric fields at frequencies above the electrode charging frequency

AC Faradaic reactions have been reported as a mechanism inducing non-ideal phenomena such as flow reversal and cell deformation in electrokinetic microfluidic systems. Prior published work described experiments in parallel electrode arrays below the electrode charging frequency (f_c), the frequency for electrical double layer charging at the electrode. However, 2D spatially non-uniform AC electric fields are required for applications such as in plane AC electroosmosis, AC electrothermal pumps, and dielectrophoresis. Many microscale experimental applications utilize AC frequencies around or above f_c. In this work, a pH sensitive fluorescein sodium salt dye was used to detect [H⁺] as an indicator of Faradaic reactions in aqueous solutions within non-uniform AC electric fields. Comparison experiments with (a) parallel (2D uniform fields) electrodes and (b) organic media were employed to deduce the electrode charging mechanism at 5 kHz (1.5f_c). Time dependency analysis illustrated that Faradaic reactions exist above the theoretically predicted electrode charging frequency. Spatial analysis showed [H⁺] varied spatially due to electric field non-uniformities and local pH changed at length scales greater than 50 μm away from the electrode surface. Thus, non-uniform AC fields yielded spatially varied pH gradients as a direct consequence of ion path length differences while uniform fields did not yield pH gradients; the latter is consistent with prior published data. Frequency dependence was examined from 5 kHz to 12 kHz at 5.5 V_pp potential, and voltage dependency was explored from 3.5 to 7.5 V_pp at 5 kHz. Results suggest that Faradaic reactions can still proceed within electrochemical systems in the absence of well-established electrical double layers. This work also illustrates that in microfluidic systems, spatial medium variations must be considered as a function of experiment time, initial medium conditions, electric signal potential, frequency, and spatial position.     

An integrated platform enabling optogenetic illumination of Caenorhabditis elegans neurons and muscular force measurement in microstructured environments

Optogenetics has been recently applied to manipulate the neural circuits of Caenorhabditis elegans (C. elegans) to investigate its mechanosensation and locomotive behavior, which is a fundamental topic in model biology. In most neuron-related research, free C. elegans moves on an open area such as agar surface. However, this simple environment is different from the soil, in which C. elegans naturally dwells. To bridge up the gap, this paper presents integration of optogenetic illumination of C. elegans neural circuits and muscular force measurement in a structured microfluidic chip mimicking the C. elegans soil habitat. The microfluidic chip is essentially a ∼1 × 1 cm² elastomeric polydimethylsiloxane micro-pillar array, configured in either form of lattice (LC) or honeycomb (HC) to mimic the environment in which the worm dwells. The integrated system has four key modules for illumination pattern generation, pattern projection, automatic tracking of the worm, and force measurement. Specifically, two optical pathways co-exist in an inverted microscope, including built-in bright-field illumination for worm tracking and pattern generation, and added-in optogenetic illumination for pattern projection onto the worm body segment. The behavior of a freely moving worm in the chip under optogenetic manipulation can be recorded for off-line force measurements. Using wild-type N2 C. elegans, we demonstrated optical illumination of C. elegans neurons by projecting light onto its head/tail segment at 14 Hz refresh frequency. We also measured the force and observed three representative locomotion patterns of forward movement, reversal, and omega turn for LC and HC configurations. Being capable of stimulating or inhibiting worm neurons and simultaneously measuring the thrust force, this enabling platform would offer new insights into the correlation between neurons and locomotive behaviors of the nematode under a complex environment.     

Coaxial flow focusing in poly(dimethylsiloxane) microfluidic devices

We have developed a coaxial flow focusing geometry that can be fabricated using soft lithography in poly(dimethylsiloxane) (PDMS). Like coaxial flow focusing in glass capillary microfluidics, our geometry can form double emulsions in channels with uniform wettability and of a size much smaller than the channel dimensions. However, In contrast to glass capillary coaxial flow focusing, our geometry can be fabricated using lithographic techniques, allowing it to be integrated as the drop making unit in parallel drop maker arrays. Our geometry enables scalable formation of emulsions down 7 μm in diameter, in large channels that are robust against fouling and clogging.     

Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Susceptibility to Alcohol Dependence

Catechol-O-methyl transferase (COMT) enzyme catalyzes the metabolism of dopamine and other catechols in the brain. Several articles investigated catechol-O-methyltransferase (COMT) Val158Met polymorphism as risk factor for alcohol dependence (AD) but the results were inconclusive. The aim of present meta-analysis was to evaluate the association of Val158Met (COMT) polymorphism with AD. Authors performed keyword search of the 4 electronic databases—Pubmed, Google Scholar, Springer Link and Science Direct databases up to December 31, 2019. Total eighteen studies that investigated the association of Val158Met polymorphism with AD were retrieved. The pooled results from the meta-analysis (2278 AD cases and 3717 healthy controls) did not show association with AD using all 5 genetic models (allele contrast model: OR = 1.02, 95% CI = 0.90–1.14, p = 0.03; homozygote model: OR = 1.06, 95% CI = 0.81–1.38, p = 0.69; dominant model: OR = 0.99, 95% CI = 0.85–1.14, p = 0.87; co-dominant model: OR = 0.97, 95% CI = 0.86–1.11, p = 0.71; recessive model: OR = 1.05;95% CI = 0.85–1.29, p = 0.61). Results of subgroup analysis showed that Val158Met is not risk for AD in Asian and Caucasian population. In conclusion, COMT Val158Met is not a risk factor for alcohol dependence.     

Reconfigurable microfluidics combined with antibody microarrays for enhanced detection of T-cell secreted cytokines

Cytokines are small proteins secreted by leukocytes in blood in response to infections, thus offering valuable diagnostic information. Given that the same cytokines may be produced by different leukocyte subsets in blood, it is beneficial to connect production of cytokines to specific cell types. In this paper, we describe integration of antibody (Ab) microarrays into a microfluidic device to enable enhanced cytokine detection. The Ab arrays contain spots specific to cell-surface antigens as well as anti-cytokine detection spots. Infusion of blood into a microfluidic device results in the capture of specific leukocytes (CD4 T-cells) and is followed by detection of secreted cytokines on the neighboring Ab spots using sandwich immunoassay. The enhancement of cytokine signal comes from leveraging the concept of reconfigurable microfluidics. A three layer polydimethylsiloxane microfluidic device is fabricated so as to contain six microchambers (1 mm × 1 mm × 30 μm) in the ceiling of the device. Once the T-cell capture is complete, the device is reconfigured by withdrawing liquid from the channel, causing the chambers to collapse onto Ab arrays and enclose cell/anti-cytokine spots within a 30 nl volume. In a set of proof-of-concept experiments, we demonstrate that ∼90% pure CD4 T-cells can be captured inside the device and that signals for three important T-cell secreted cytokines, tissue necrosis factor-alpha, interferon-gamma, and interleukin-2, may be enhanced by 2 to 3 folds through the use of reconfigurable microfluidics.     

Frequency sweep rate dependence on the dielectrophoretic response of polystyrene beads and red blood cells

Alternating current (AC) dielectrophoresis (DEP) experiments for biological particles in microdevices are typically done at a fixed frequency. Reconstructing the DEP response curve from static frequency experiments is laborious, but essential to ascertain differences in dielectric properties of biological particles. Our lab explored the concept of sweeping the frequency as a function of time to rapidly determine the DEP response curve from fewer experiments. For the purpose of determining an ideal sweep rate, homogeneous 6.08 μm polystyrene (PS) beads were used as a model system. Translatability of the sweep rate approach to ∼7 μm red blood cells (RBC) was then verified. An Au/Ti quadrapole electrode microfluidic device was used to separately subject particles and cells to 10Vpp AC electric fields at frequencies ranging from 0.010 to 2.0 MHz over sweep rates from 0.00080 to 0.17 MHz/s. PS beads exhibited negative DEP assembly over the frequencies explored due to Maxwell-Wagner interfacial polarizations. Results demonstrate that frequency sweep rates must be slower than particle polarization timescales to achieve reliable incremental polarizations; sweep rates near 0.00080 MHz/s yielded DEP behaviors very consistent with static frequency DEP responses for both PS beads and RBCs.     

Influence of buoyancy-driven flow on mass transfer in a two-stream microfluidic channel: Introduction of cryoprotective agents into cell suspensions

A variety of methods have been used to introduce chemicals into a stream or to mix two or more streams of different compositions using microfluidic devices. In the following paper, the introduction of cryoprotective agents (CPAs) used during cryopreservation of cells in order to protect them from freezing injuries and increase viability post thaw is described. Dimethylsulphoxide (DMSO) is the most commonly used CPA. We aim to optimize the operating conditions of a two-stream microfluidic device to introduce a 10% vol/vol solution of DMSO into a cell suspension. Transport behavior of DMSO between two streams in the device has been experimentally characterized for a spectrum of flow conditions (0.7 < Re < 10), varying initial donor stream concentrations, (1% vol/vol < C_o < 15% vol/vol) and different flow rate fractions (0.23 < f_q < 0.77). The outlet cell stream concentration is analyzed for two different flow configurations: one with the cell stream flowing on top of the DMSO-rich donor stream, and the other with the cell stream flowing beneath the heavy DMSO-laden stream. We establish a transition from a diffusive mode of mass transfer to gravity-influenced convective currents for Atwood numbers (A_t) in the range of (1.7 × 10⁻³ < A_t < 3.1 × 10⁻³) for the latter configuration. Flow visualization with cells further our understanding of the effect of A_t on the nature of mass transport. Cell motion studies performed with Jurkat cells confirm a high cell recovery from the device while underscoring the need to collect both the streams at the outlet of the device and suggesting flow conditions that will help us achieve the target DMSO outlet concentration for clinical scale flow rates of the cell suspension.     

Embryo formation from low sperm concentration by using dielectrophoretic force

A biochip system imitates the oviduct of mammals with a microfluidic channel to achieve fertilization in vitro of imprinting-control-region (ICR) mice. We apply a method to manipulate and to position the oocyte and the sperm of ICR mice at the same time in our microfluidic channel with a positive dielectrophoretic (DEP) force. The positive dielectrophoretic response of the oocyte and sperm was exhibited under applied bias conditions AC 10 V_pp waveform, 1 MHz, 10 min. With this method, the concentration of sperm in the vicinity of the oocyte was increased and enhanced the probability of natural fertilization. We used commercial numerical software (CFDRC-ACE+) to simulate the square of the electric field and analyzed the location at which the oocyte and sperm are trapped. The microfluidic devices were designed and fabricated with poly(dimethylsiloxane). The results of our experiments indicate that a positive DEP served to drive the position of the oocyte and the sperm to natural fertilization (average rate of fertilization 51.58%) in our microchannel structures at insemination concentration 1.5 × 10⁶ sperm ml⁻¹. Embryos were cultured to two cells after 24 h and four cells after 48 h.     

Spatially variant red blood cell crenation in alternating current non-uniform fields

Alternating-current (AC) electrokinetics involve the movement and behaviors of particles or cells. Many applications, including dielectrophoretic manipulations, are dependent upon charge interactions between the cell or particle and the surrounding medium. Medium concentrations are traditionally treated as spatially uniform in both theoretical models and experiments. Human red blood cells (RBCs) are observed to crenate, or shrink due to changing osmotic pressure, over 10 min experiments in non-uniform AC electric fields. Cell crenation magnitude is examined as functions of frequency from 250 kHz to 1 MHz and potential from 10 V_pp to 17.5 V_pp over a 100 μm perpendicular electrode gap. Experimental results show higher peak to peak potential and lower frequency lead to greater cell volume crenation up to a maximum volume loss of 20%. A series of experiments are conducted to elucidate the physical mechanisms behind the red blood cell crenation. Non-uniform and uniform electrode systems as well as high and low ion concentration experiments are compared and illustrate that AC electroporation, system temperature, rapid temperature changes, medium pH, electrode reactions, and convection do not account for the crenation behaviors observed. AC electroosmotic was found to be negligible at these conditions and AC electrothermal fluid flows were found to reduce RBC crenation behaviors. These cell deformations were attributed to medium hypertonicity induced by ion concentration gradients in the spatially nonuniform AC electric fields.     

A capillary dielectrophoretic chip for real-time blood cell separation from a drop of whole blood

This study proposes a capillary dielectrophoretic chip to separate blood cells from a drop of whole blood (approximately 1 μl) sample using negative dielectrophoretic force. The separating efficiency was evaluated by analyzing the image before and after dielectrophoretic force manipulation. Blood samples with various hematocrits (10%–60%) were tested with varied separating voltages and chip designs. In this study, a chip with 50 μm gap design achieved a separation efficiency of approximately 90% within 30 s when the hematocrit was in the range of 10%–50%. Furthermore, glucose concentration was electrochemically measured by separating electrodes following manipulation. The current response increased significantly (8.8-fold) after blood cell separation, which was attributed not only to the blood cell separation but also to sample disturbance by the dielectrophoretic force.     

Poly(vinyl alcohol)-heparin biosynthetic microspheres produced by microfluidics and ultraviolet photopolymerisation

Biosynthetic microspheres have the potential to address some of the limitations in cell microencapsulation; however, the generation of biosynthetic hydrogel microspheres has not been investigated or applied to cell encapsulation. Droplet microfluidics has the potential to produce more uniform microspheres under conditions compatible with cell encapsulation. Therefore, the aim of this study was to understand the effect of process parameters on biosynthetic microsphere formation, size, and morphology with a co-flow microfluidic method. Poly(vinyl alcohol) (PVA), a synthetic hydrogel and heparin, a glycosaminoglycan were chosen as the hydrogels for this study. A capillary-based microfluidic droplet generation device was used, and by varying the flow rates of both the polymer and oil phases, the viscosity of the continuous oil phase, and the interfacial surface tension, monodisperse spheres were produced from ∼200 to 800 μm. The size and morphology were unaffected by the addition of heparin. The modulus of spheres was 397 and 335 kPa for PVA and PVA/heparin, respectively, and this was not different from the bulk gel modulus (312 and 365 for PVA and PVA/heparin, respectively). Mammalian cells encapsulated in the spheres had over 90% viability after 24 h in both PVA and PVA/heparin microspheres. After 28 days, viability was still over 90% for PVA-heparin spheres and was significantly higher than in PVA only spheres. The use of biosynthetic hydrogels with microfluidic and UV polymerisation methods offers an improved approach to long-term cell encapsulation.     

Gold coated optical fibers as three-dimensional electrodes for microfluidic enzymatic biofuel cells: Toward geometrically enhanced performance

For the first time, we report on the preliminary evaluation of gold coated optical fibers (GCOFs) as three-dimensional (3D) electrodes for a membraneless glucose/O₂ enzymatic biofuel cell. Two off-the-shelf 125 μm diameter GCOFs were integrated into a 3D microfluidic chip fabricated via rapid prototyping. Using soluble enzymes and a 10 mM glucose solution flowing at an average velocity of 16 mm s⁻¹ along 3 mm long GCOFs, the maximum power density reached 30.0 ± 0.1 μW cm⁻² at a current density of 160.6 ± 0.3 μA cm⁻². Bundles composed of multiple GCOFs could further enhance these first results while serving as substrates for enzyme immobilization.     

Microfluidic size separation of cells and particles using a swinging bucket centrifuge

Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency.     

Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel

Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (μ_Blood/μ_PBS) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (Q_PBS^SS/Q_Blood^L). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formula (A_Blood (t) = A_α + A_β exp [−(t − t₀)/λ_Blood]) is selected based on the pressure difference (ΔP = P_A − P_B) at each junction (A, B) of both side channels. The characteristic time of blood (λ_Blood) is measured by analyzing the area (A_Blood) filled with blood in the bridge channel by selecting an appropriate detection window in the microscopic images captured by a high-speed camera (frame rate = 200 Hz, total measurement time = 7 s). The elasticity of blood (G_Blood) is identified using the relationship between the characteristic time and the viscosity of blood. For practical demonstrations, the proposed method is successfully applied to evaluate the variations in viscosity and elasticity of various blood samples: (a) various hematocrits form 20% to 50%, (b) thermal-induced treatment (50 °C for 30 min), (c) flow-induced shear stress (53 ± 0.5 mL/h for 120 min), and (d) normal rat versus spontaneously hypertensive rat. Based on these experimental demonstrations, the proposed method can be effectively used to monitor variations in viscosity and elasticity of bloods, even with the absence of fully integrated sensors, tedious labeling and calibrations.     

Micromixing visualization and quantification in a microscale multi-inlet vortex nanoprecipitation reactor using confocal-based reactive micro laser-induced fluorescence

A technique for visualizing and quantifying reactive mixing for laminar and turbulent flow in a microscale chemical reactor using confocal-based microscopic laser induced fluorescence (confocal μ-LIF) was demonstrated in a microscale multi-inlet vortex nanoprecipitation reactor. Unlike passive scalar μ-LIF, the reactive μ-LIF technique is able to visualize and quantify micromixing effects. The confocal imaging results indicated that the flow in the reactor was laminar and steady for inlet Reynolds numbers of 10, 53, and 93. Mixing and reaction were incomplete at each of these Reynolds numbers. The results also suggested that although mixing by diffusion was enhanced near the midplane of the reactor at Re_j = 53 and 93 due to very thin bands of acidic and basic fluid forming as the fluid spiraled towards the center of the reactor, near the top, and bottom walls of the reactor, the lower velocities due to fluid friction with the walls hindered the formation of these thin bands, and, thus, resulted in large regions of unmixed and unreacted fluid. At Re_j = 240, the flow was turbulent and unsteady. The mixing and reaction processes were still found to be incomplete even at this highest Reynolds number. At the reactor midplane, the flow images at Re_j = 240 showed unmixed base fluid near the center of the reactor, suggesting that just as in the Re_j = 53 and 93 cases, lower velocities near the top and bottom walls of the reactor hinder the mixing and rection of the acidic and basic streams. Ensemble averages of line-scan profiles for the Re_j = 240 were then calculated to provide statistical quantification of the microscale mixing in the reactor. These results further demonstrate that even at this highest Reynolds number investigated, mixing and reaction are incomplete. Visualization and quantification of micromixing using this reactive μ-LIF technique can prove useful in the validation of computational fluid dynamics models of micromixing within microscale chemical reactors.     

Formation of lipid bilayer membrane in a poly(dimethylsiloxane) microchip integrated with a stacked polycarbonate membrane support and an on-site nanoinjector

This paper describes a new and facile approach for the formation of pore-spanning bilayer lipid membranes (BLMs) within a poly(dimethylsiloxane) (PDMS) microfluidic device. Commercially, readily available polycarbonate (PC) membranes are employed for the support of BLMs. PC sheets with 5 μm, 2 μm, and 0.4 μm pore diameters, respectively, are thermally bonded into a multilayer-stack, reducing the pore density of 0.4 μm-pore PC by a factor of 200. The BLMs on this support are considerably stable (a mean lifetime: 17 h). This multilayer-stack PC (MSPC) membrane is integrated into the PDMS chip by an epoxy bonding method developed to secure durable bonding under the use of organic solvents. The microchip has a special channel for guiding a micropipette in the proximity of the MSPC support. With this on-site injection technique, tens to hundreds of nanoliters of solutions can be directly dispensed to the support. Incorporating gramicidin ion channels into BLMs on the MSPC support has confirmed the formation of single BLMs, which is based on the observation from current signals of 20 pS conductance that is typical to single channel opening. Based on the bilayer capacitance (1.4 pF), about 15% of through pores across the MSPC membrane are estimated to be covered with BLMs.     

Dielectrophoresis based discrimination of human embryonic stem cells from differentiating derivatives

Assessment of the dielectrophoresis (DEP) cross-over frequency (f_xo), cell diameter, and derivative membrane capacitance (C_m) values for a group of undifferentiated human embryonic stem cell (hESC) lines (H1, H9, RCM1, RH1), and for a transgenic subclone of H1 (T8) revealed that hESC lines could not be discriminated on their mean f_xo and C_m values, the latter of which ranged from 14 to 20 mF/m². Differentiation of H1 and H9 to a mesenchymal stem cell-like phenotype resulted in similar significant increases in mean C_m values to 41–49 mF/m² in both lines (p < 0.0001). BMP4-induced differentiation of RCM1 to a trophoblast cell-like phenotype also resulted in a distinct and significant increase in mean C_m value to 28 mF/m² (p < 0.0001). The progressive transition to a higher membrane capacitance was also evident after each passage of cell culture as H9 cells transitioned to a mesenchymal stem cell-like state induced by growth on a substrate of hyaluronan. These findings confirm the existence of distinctive parameters between undifferentiated and differentiating cells on which future application of dielectrophoresis in the context of hESC manufacturing can be based.     

Genetic Variant XRCC1 rs1799782 (C194T) and Risk of Cancer Susceptibility in Indian Population: A Meta-analysis of Case–Control Studies

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. Several studies have reported contradictory results for XRCC1 exon 6 C>T (rs1799782) gene polymorphism and cancer risk in Indian population has provided inconsistent results. Therefore, we have performed this meta-analysis to evaluate the relationship between XRCC1 exon 6 C>T gene polymorphism and risk of cancer by published studies. We searched PubMed and Google scholar web databases to cover all studies published on association between XRCC1 exon 6 C>T gene polymorphism and cancer risk. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. In order to derive a more precise estimation of the association, A total of 3197 confirmed cancer cases and 3819 controls were included from eligible seventeen case-controls studies. Results from overall pooled analysis demonstrated suggested that that variant allele (T vs. C: OR 1.301, 95% CI 1.003–1.688, p = 0.047) was associated with the risk of overall cancer. Other genetic models; heterozygous (TC vs. CC: OR 1.108, 95% CI 0.827–1.485, p = 0.491), homozygous (TT vs. CC: OR 1.479, 95% CI 0.877–2.493, p = 0.142), dominant (TT+TC vs. CC: OR 1.228, 95% CI 0.899–1.677, p = 0.196) and recessive (TT vs. TC+CC: OR 1.436, 95% CI 0.970–2.125, p = 0.071) did not reveal statistical association. Publication bias observation was also considered and none was detected during the analysis. The present meta-analysis suggested that the variant allele T of XRCC1 exon 6 gene polymorphism was associated with the risk of cancer. It is therefore pertinent to confirm this finding in a large sample size to divulge the mechanism of this polymorphism and cancer risk in Indian population.