Homozygote Genotype Research Articles

Lack of association between potential prothrombotic genetic risk factors and arterial and venous thrombosis.

Recent studies have shown an association between thrombosis and factor VII (FVII), tissue factor (TF), and angiotensin-converting enzyme (ACE). This suggests that individuals with FVII-402 G/A, FVII-401 G/T, TF+5466 A/G, and ACE-287 insertion/deletion (I/D) polymorphisms present an increased risk of venous thrombosis, heart disease, and ischemic stroke compared with controls. In this study, we investigated the frequencies of these polymorphisms and their association with arterial and venous thrombosis. For the FVII-402 G/A polymorphism, there were 57.3% heterozygote (HT) genotypes and 8.3% homozygote (HM) genotypes in the patients, and 45.2% HT genotypes and 15.4% HM genotypes in the controls. For the FVII-401 G/T polymorphism, there were 37.5% HT genotypes and 3.1% HM genotypes in the patients, and 32.7% HT genotypes and 4.8% HM genotypes in the controls. The polymorphism TF+5466 A/G was not found in any of the samples analyzed. For the ACE-287 I/D polymorphism, there were 43 (40.6%) HT genotypes and 63 (59.4%) HM genotypes in the controls and 28 (45.2%) HT genotypes and 34 (54.8%) HM genotypes in the patients. No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.

DNA sequence polymorphism within the bovine adenosine monophosphate deaminase 1 (AMPD1) is associated with production traits in Chinese cattle.

The objectives of the present study were to detect an 18-bp deletion mutation in the bovine adenosine monophosphate deaminase 1 (AMPD1) gene and analyze its effect on growth traits in 2 Chinese cattle breeds using DNA sequencing and agarose electrophoresis. The five 19-bp polymerase chain reaction products of the AMPD1 gene exhibited 3 genotypes and 2 alleles: WW: homozygote genotype (wild-type); DD: homozygote genotype (mutant-type); WD: heterozygote genotype. Frequencies of the W allele varied from 66.15-70.35%. The associations between the 18-bp deletion mutation in the AMPD1 gene with production traits in 226 Jia-Xian red cattle was analyzed. The animals with genotype WW showed significantly higher heart girth and body weight than those with genotypes WD and DD at 24 months (P < 0.01). Our results indicate that the deletion mutation in the AMPD1 gene is associated with production traits, and may be used for marker-assisted selection in beef cattle breeding programs.

MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population.

MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.

DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture.

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%, p = 0.049; 38.15% versus 16.2%, p = 0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863; p = 0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129; p = 0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992; p = 0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

Association between Estrogen Receptor-α Gene XbaI and PvuII Polymorphisms and Periodontitis Susceptibility: A Meta-Analysis.

Background. Certain studies have previously explored the association between the estrogen receptor-α (ER-α) gene polymorphisms and periodontitis susceptibility, although the current results are controversial. The present study, using meta-analysis, aimed to investigate the nature of the genetic susceptibility of the ER-α for developing periodontitis. Methods. A comprehensive literature search of PubMed, Embase, CNKI, and Wanfang databases was conducted up to January 8, 2015. Statistical manipulation was performed using Stata version 13.0 software. Odds ratios (ORs) and corresponding 95% confident intervals (CIs) were calculated to estimate the association in five genetic models. Results. A total of 17 eligible case-control studies from seven identified publications consisting of nine studies for the XbaI polymorphism and eight studies for the PvuII polymorphism were included in the meta-analysis. We found elevated risk of periodontitis in XbaI XX genotype carriers. Moreover, subgroup analyses demonstrated increased risk for chronic periodontitis of XbaI XX genotype carriers, specifically in the Chinese Han female population. No significant association was observed between PvuII polymorphism and periodontitis. Conclusion. Current evidence indicated that the homozygote (XX) genotype of ER-α gene XbaI polymorphism, but not PvuII mutation, may increase the risk of chronic periodontitis, specifically in the Chinese Han female population.

Incidence Assessment of MTHFR C677T and A1298C Polymorphisms in Iranian Non-syndromic Cleft Lip and/or Palate Patients.

Background and aims. The aim of the present study is to determine the incidence of MTHFR C677 T and A1298C muta-tions in Iranian patients with cleft lip and/or cleft palate.Materials and methods. We screened 61 Iranian patients with cleft lip and/or cleft palate for mutations in the two alleles of MTHFR gene associated with cleft lip and/or palate: A1298C and C677T, using Polymerase Chain Reaction following by RFLP.Results. The 677T and 1298C homozygote genotypes showed a frequency of 36.1% and 11.4%, respectively. Combined genotype frequencies in newborns having oral clefts showed that the highest genotype was 677TT/1298AA (22.9%) and 677TT/1298CC genotypes were not observed.Conclusion. The results showed that 65.6% of all patients had at least one T mutant allele in C677T and 58.9% C mutant allele for A1298C. According to the frequencies of homozygosity of mutant alleles, it could be said that MTHFR genotype of 677TT shows a greater role in having oral clefts.

Polymorphisms of the bovine MC3R gene and their associations with body measurement traits and meat quality traits in Qinchuan cattle.

The melanocortin 3 receptor (MC3R) gene, which belongs to the rhodopsin-like family A of the G protein-coupled receptor family, plays a crucial role in feed efficiency and energy homeostasis. The aim of this study was to examine associations between bovine MC3R gene polymorphisms and body measurement traits (BMTs) and meat quality traits (MQTs). We identified three synonymous mutations (T429C, T537C, and T663C) in exon 1 of the MC3R gene in Chinese Qinchuan beef cattle (N = 271) by sequencing. D' and r(2) values revealed that these three SNPs were in strong linkage disequilibrium (LD) (r(2) > 0.33); the T429C and T537C SNPs were in complete LD (D' = 1 and r(2) = 1). Association analyses revealed that the SNPs were significantly associated with BMTs and MQTs in Qinchuan cattle. Individuals with the wild homozygotic genotypes g.TTTT and g.TT had significantly higher values of chest depth, heart girth, back fat thickness, intramuscular fat content, and loin muscle area than the mutant heterozygotic genotypes g.TCTC and g.TC. These results suggest that the MC3R gene affects MQTs in Qinchuan cattle, and that it may be a good candidate gene for marker-assisted selection.

TGF-β1 polymorphisms and familial aggregation of liver cancer in Guangxi, China

The goal of present study was to investigate the relationship between polymorphisms of TGF-β1 and familial aggregation of liver cancer in Guangxi Zhuang, Han, and Yao populations. We conducted a population-based case-control family study of liver cancer in Guanxi, China. A total of 214 individuals from 37 case families were surveyed for polymorphisms in TGF-β1. We genotyped six functional TGF-β1 polymorphisms: rs1800469, rs2241715, rs2241716, rs11466345, rs8105161, and rs747857. Levels of TGF-β1, hepatitis B surface antigen, and anti-hepatitis C virus in all serum samples were detected using the enzyme-linked immunoassay method, and presence of hepatitis B virus (HBV) DNA was determined using polymerase chain reaction amplification. A standardized questionnaire was used to collect information from subjects, including alcohol consumption, smoking, eating, and water drinking habits. The results were compared with those from 214 control individuals. The results showed that the TGF-β1 genotypes rs1800469, rs2241715, rs2241715, and rs8105161 were more frequent in patients than in controls. The risk factors for familial aggregation of liver cancer in Guangxi were determined, from high to low, to be: drinking sugared beverages > alcohol consumption > HBV DNA-positive > rs1800469 TT homozygous genotype > rs2241715 TT homozygous genotype. The results suggested that TGF-β1 rs1800469 TT and rs2241715 TT homozygote genotypes represent the genetic factors underlying familial clustering of liver cancer in Guangxi, and that drinking water use, alcohol consumption, and testing positive for HBV DNA are the main environmental factors contributing to familial aggregation of liver cancer in Guangxi.

Polymorphism of p53 gene codon 72 in endometrial cancer: correlation with tumor grade and histological type.

Endometrial cancer is the fourth most common cancer among women in developed countries. Patients with endometrial cancer may benefit from systemic chemotherapy alone or in combination with targeted therapies if the disease is clinically diagnosed prior to spread and metastasis to other organs. The aim of this study was to evaluate the prognostic role of p53 polymorphism and its correlation with tumor grade in human uterine endometrial carcinomas. A total of 75 patients with endometrial carcinomas were studied for possible mutations in exon 4 of the p53 gene using polymerase chain reaction and restricting fragment length polymorphism techniques and sequencing. In recent study, The rate of homozygote genotype of pro/pro or Arg/Arg in high grade group was higher than in comparison with low grade one. In addition samples that were undigested in RFLP, showed mutation in exone 4. Our findings showed that high grade endometrial carcinomas are highly associated with TP53 polymorphisms in comparison with low grades.

The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Myeloid Leukemia Risk in Turkish Patients

Interleukin-18 (IL-18) is a cytokine which belongs to the interleukin-1 superfamily and secreted by various immune and non-immune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between -137G/C (rs187238) IL-18 gene polymorphism and susceptibility to chronic myelogenous leukemia(CML) in Turkish patients. The frequencies of polymorphism -137G/C were studied in thirty chronic myelogenous and thirty healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. Significant associations were detected between the IL-18 rs187238 (G/C) polymorphism and CML patients. A higher prevalence of the C allele was found in CML cases with respect to controls (p<0.05). The GC heterozygote and CC homozygote genotypes are associated with the risk of CML when compared with controls (OR, 1.9023; 95% CI, 0.6171-5.8636 for GC genotype and OR, 10.3585; 95% CI, 0.5326-201.4622 for CC genotype). These results indicate that individuals that are either heterozygote (GC) or homozygote for CC genotype are associated with the development of chronic myelogenous leukemia in Turkish population. Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings. DisclosuresNo relevant conflicts of interest to declare.

Association of Toll like receptor Asp299Gly with rheumatoid arthritis risk: A systematic review of case–control studies and meta-analysis

ObjectiveRheumatoid arthritis (RA) is thought to be triggered by various genetic and environmental factors. Few human epidemiologic studies demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are associated with RA. We aimed to evaluate the effects of TLR polymorphisms on the risk of RA pathogenesis by using a meta-analysis approach. MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature was conducted. We screened the medical literature based on keywords search in MEDLINE and EMBASE ‘Toll-like receptor’, ‘polymorphism’, and rheumatoid arthritis. Meta-analyses were performed under the random-effects model by using: (1) recessive, (2) homozygous, (3) dominant, (4) codominant and allele contrast models. ResultsA total of 3086 cases and 3756 controls in nine studies were included in the meta-analysis. Association between TLR4 Asp299Gly and RA risk was marginally significant [OR=0.856 (95% CI, 0.716–1.022); P=0.086] in the homozygous model. AA and GG homozygote genotypes tended to be significant protective factors against RA risk. ConclusionOur overall analyses indicated that TLR4 Asp299Gly polymorphism might contribute to RA pathogenesis.

Involvement of anandamide transporter in calcitonin gene-related peptide expression stimulated by nitroglycerin and influence of ALDH2 Glu504Lys polymorphism.

The aim of this study was to investigate whether N-arachidonic acid ethanolamine (anandamide, AEA) transporter contributed to calcitonin gene-related peptide (CGRP) expression mediated by nitroglycerin (GTN) in peripheral blood mononuclear cells (PBMCs) of healthy volunteers and its association with the mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism. In 10 ALDH2*2-genotyped Chinese volunteers, we assessed the activity of AEA transporter and expression of CGRP messenger ribonucleic acid (mRNA) in cultured PBMCs treated with different concentration of GTN with or without pretreatment with AM404 (the AEA transporter blocker). In this study, the activity of AEA transporter and expression of CGRP mRNA elevated with the increase in the concentration of GTN. Pretreatment of the cells with AM404 (1 μM) 2 hours before GTN reduced the GTN-induced increase in both AEA transporter activity and CGRP mRNA expression significantly, and cells with the ALDH2*1/*1 homozygote genotype showed significantly higher activity of AEA transporter and CGRP mRNA expression than carriers of the ALDH2*2 allele. Therefore, we strongly suggested that GTN can stimulate CGRP expression by elevating the AEA transporter activity, which is affected by ALDH2 Glu504Lys polymorphism.

Dopamine D3 receptor Ser9Gly and catechol-o-methyltransferase Val158Met polymorphisms and acute pain in sickle cell disease.

Pain in sickle cell disease (SCD) is characterized by episodes of acute pain, primarily responsible for acute health care utilization, and persistent chronic pain. Pain severity and frequency vary significantly among patients with SCD. In this study, we investigated the possible contribution of monoamine gene polymorphisms to pain variation. Adult subjects with SCD completed PAINReportIt, a computerized McGill Pain Questionnaire, from which we calculated the Composite Pain Index. Utilization data were obtained from the medical record and biweekly telephone calls for 12 months. Utilization is defined as admissions to the emergency department and/or the acute care center resulting from a sickle cell pain crisis. We performed genotyping for catechol-O-methyltransferase (COMT) Val158Met (rs4680) and dopamine D3 receptor (DRD3) Ser9Gly (rs6280) polymorphisms, which were analyzed for associations with pain phenotypes. Binary logistic models revealed that DRD3 Ser9Gly heterozygote patients were more likely not to have an acute pain crisis (odds ratio [OR] [95% confidence interval {CI}], 4.37 [1.39-22.89]; P = 0.020), which remained so when demographic variables were considered (OR [95% CI], 4.53 [1.41-28.58]; P = 0.016). COMT Val158Met Met allele showed lower probability for zero utilization (OR [95% CI], 0.32 [0.12-0.83]; P = 0.020) than the Val allele. In the negative binomial regression analysis, subjects with COMT Met/Met genotype had utilization incident rate ratio (95% CI) of 2.20 (1.21-3.99) over those with Val/Val (P = 0.010). These exploratory findings suggest that DRD3 Ser9Gly and COMT Val158Met may contribute to pain heterogeneity in SCD, as suggested by the different rates of acute pain crisis. Specifically, SCD patients with the DRD3 homozygote genotypes, COMT 158 Met allele or Met/Met genotype, are more likely to have acute care utilization, an indicator of acute pain. These results, however, will need to be further examined in future large prospective studies.

Methylenetetrahydrofolate reductase C667T polymorphism is associated with increased risk of coronary artery disease in a Chinese population.

Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix metalloproteinases (MMPs)-2, tumour necrosis factor (TNF)-α, macrophage migration inhibitory factor (MIF) rs755622G/C and cyclin D1 (CCND1) rs678653G/C contribute to CAD susceptibility. We examined the association between the five polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS). When the MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT genotypes were associated with a significantly increased risk for CAD. The CT heterozygote genotype was not associated with the risk for CAD. Logistic regression analyses revealed that MMP-2 rs243865 C/T, TNF-α rs1800629 A/G, MIF rs755622G/C and CCND1 rs678653G/C polymorphisms were not associated with the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism is associated with CAD development. Future larger studies with other ethnic populations are required to confirm current findings.

Uracil-DNA glycosylase (UNG) rs246079 G/A polymorphism is associated with decreased risk of esophageal cancer in a Chinese population.

Esophageal cancer is the sixth leading cause of cancer-associated death worldwide. In addition to environmental risk factors, genetic factors might play an important role in esophageal cancer carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between functional single nucleotide polymorphisms (SNPs) in uracil-DNA glycosylase (UNG) and the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The UNG rs3219218 A/G and UNG rs246079 G/A genotypes were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the UNG rs246079 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly decreased risk for ESCC (GA vs. GG: adjusted OR 0.67, 95 % CI 0.49-0.91, P = 0.011); the AA genotype was not associated with the risk of ESCC. In stratification analyses, a significantly decreased risk of ESCC associated with the UNG rs246079 G/A polymorphism was evident among women, younger patients and never-smokers and never-drinkers. The UNG rs3219218 A/G polymorphism was not associated with the risk for ESCC. These findings indicated that UNG rs246079 G/A might contribute to a decreased risk of ESCC in specific populations. Because of the limited sample size, further studies including a larger and more diverse population, as well as tissue-specific biological characterization, are required to confirm the current findings.

Genetic diversity of Romanian Grey Steppe cattle based on milk protein polymorphism

s / Journal of Biotechnology 185S (2014) S37–S125 S49 in the studied digestive organs. Results showed the possibility of using the “Ingo-2” in the practical medicine as a new nanosorbent. http://dx.doi.org/10.1016/j.jbiotec.2014.07.163 A new CT procedure for the study of the elbow in the dog Carla Murino1,∗, Giuseppina Mennonna1, Bruna Santangelo2, Francesco Lamagna2, Caterina Balestriere2, Leonardo Meomartino1 1 Radiology Veterinary Centre of University of Naples Federico II, Naples, Italy 2 Department of Veterinary Medicine and Animal Production of University of Naples Federico II, Naples, Italy E-mail address: carlamurino@gmail.com (C. Murino). Introduction: Previous described canine elbow-CT procedures need the head pulled laterally and caudally. This positioning is stressful for the neck and potentially dangerous in breeds prone to the Wobbler syndrome.Aim: Todevelop anewnon-stressful procedure for canine elbow-CT. Materials and methods: Prospectively, from January 2013, two elbow-CT procedures were used. The described procedure (DP): sternal recumbency with laterally and caudally pulled head and cranially extended forelimbs. The new procedure (NP): lateral recumbency, with forelimbs cranially pulled, very close one to each other and to the neck, in order to obtain the smallest field of view (FOV) and mean pixel dimension (MPD). CT procedures were compared for spatial resolution and presence of artefacts. Results: 18 elbows, from9dogs,were included.Mean FOV was: NP 126.6mm (±14.1); DP 103.3 (±5.16); mean MPD was: NP 0.25mm (±0.03); DP 0.21mm (±0.01). FOV and MPD were significantly larger inNP. Streak artefactswere absent in both procedures. Discussion and conclusion: compared to the DP, the NP has a significantly larger FOV and MPD, but a simpler and safer positioning, without streak artefacts. Furthermore, NP permits a more symmetrical positioning of the elbows and therefore to visualize them simultaneously. http://dx.doi.org/10.1016/j.jbiotec.2014.07.164 Genetic diversity of Romanian Grey Steppe cattle based on milk protein polymorphism Daniela Elena Ilie1,∗, Steofil Creanga2, Andrei Cristian Gradinaru3, Silviu Ionut Bors2, Dan Lucian Dascalu2, David Chirila4, Ada Cean1 1 Research and Development Station for Bovine, Arad, Romania 2 Research and Development Station for Bovine, Iasi, Romania 3 University of Agricultural Sciences and Veterinary Medicine of Iasi, Iasi, Romania 4 Banat’s University of Agricultural Sciences and Veterinary Medicine “King Michael I of Romania” from Timisoara, Timisoara, Romania E-mail address: danailie@yahoo.com (D.E. Ilie). The aim of this study was to determine the polymorphism of the most important lacto-proteins in Romanian Grey Steppe breed, currently included in a genetic resource preservation program. DNA samples from55RomanianGrey Steppe individuals, including six bulls, were genotyped for kappa-casein ( -CN) and betalactoglobulin ( -LG) and only 50 samples for alpha-lactalbumin ( -LA), using the PCR-RFLP technique. The allele and genotype frequencies were calculated by direct counting, and the HardyWeinberg equilibrium was tested using the chi-square test ( 2). In addition, the homozygosity coefficient, based on homozygotic genotype frequencies,was statistically interpreted.AandBvariants were identified for -CN and -LG, whereas only the B allele was identified for -LA. The frequencies for A and B alleles were 0.464 and 0.536 for -CN, and 0.409 and 0.591 for -LG, respectively. The AB genotype was the most prevalent for both -CN and -LG (0.491 and 0.564), whereas the AA genotype displayed the lowest frequencies (0.218 and 0.127) for the same proteins. The results of the chi-square test for Hardy-Weinberg equilibrium showed that the investigated individuals are in genetic equilibrium. The calculated homozygosity coefficientwas 22.03%,which is representative for every Hardy-Weinberg population. Acknowledgements This work was financed through PNII-PCCA-120/2012 program. http://dx.doi.org/10.1016/j.jbiotec.2014.07.165 Using geographical information system for spatial evaluation of canine disc herniations Constantin Daraban1, Carla Murino2,∗, Giuseppe Marzatico2, Giuseppina Mennonna2, Gerardo Fatone2, Fabiana Micieli 2, Vasile Vulpe1, Leonardo Meomartino2 1 Faculty of Veterinary Medicine, Iasi, Romania 2 Department of Veterinary Medicine and Animal Production, Naples, Italy E-mail address: carlamurino@gmail.com (C. Murino). Background: Geographical Information System (GIS) is used in analyzinganddisplaying referenced information.GIS applicationshave never been reported in Veterinary Imaging. Aim: To develop a GISbased vertebral canal (VC) map useful for spatial evaluation of extruded disc herniation (EDH) in dogs. Methods: A GIS software (ArcGIS®) was used to create 2D and 3D maps in which VC surface was divided in polygons by lines representing the latitude and longitude. Depending on dislocation, EDH could be localized in one of the above regions. The actual dislocations of herniated disc material were assessed using a series of CT studies. Choropleth maps were realized based on frequency of EDH dislocation. Results: A cylindrical model of the VC with 78 latitudinal and 8 longitudinal lines dividing 624 polygons was created. Dislocation of EDH was assessed in 142 dogs with 177 EDH. Most of EDHs were located on the transitional regions (cervico-axial; cervico-thoracic; thoracolumbar; lumbo-sacral) at level of ventro-cranial and ventro-central polygons. Discussions: choropleth maps highlighted both the distribution and the dislocation pattern of EDH throughout the VC. Conclusion: GIS proved to be a valuable tool in analyzing dog’s EDH. Further studies are required for biomechanical analysis of EDH’s dislocation pattern. http://dx.doi.org/10.1016/j.jbiotec.2014.07.166

Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation

We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain.

Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies.

Background and ObjectiveA number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case-control studies was thus performed.MethodsA literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations.ResultsArg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179–2.609, I2 = 16.9%, studies = 2, case = 314, control = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417–0.769, I2 = 0.0%, studies = 11, case = 1693, control = 502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434–0.856, I2 = 0.0%, studies = 11, case = 1693, control = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768–0.971, I2 = 46.9%, n = 18, case = 3160, control = 3433).ConclusionsNone of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population.

EGF rs11568835 G/A polymorphism is associated with increased risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune rheumatological disease thought to have substantial genetic contributions. Epidermal growth factor (EGF) can activate DNA synthesis and cellular proliferation. Early RA synovial fluid was characterized by significantly elevated levels stromal cell and macrophage-related cytokines including EGF. We therefore hypothesized that EGF polymorphisms may contribute to RA susceptibility in the Chinese population. We studied EGF rs11568835 G/A and EGF rs3756261 T/C polymorphisms in 520 patients with RA and 520 controls in a Chinese population. When the EGF rs11568835 GG homozygote genotype was used as the reference group, the AA genotype was associated with an increased risk for RA (AA versus GG, odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.19–11.17, p = 0.024), the GA or GA/AA genotype was not associated with the risk for RA (GA versus GG, OR = 0.99, 95% CI = 0.75–1.31, p = 0.931; GA + AA versus GG, OR = 1.06, 95% CI = 0.81–1.40, p = 0.659). EGF rs3756261 T/C was not associated with susceptibility to RA. These results provide the first positive evidence for an association between EGF rs11568835 G/A polymorphism and RA.

TERT-CLPTM1L Rs401681 C&gt;T Polymorphism Was Associated with a Decreased Risk of Esophageal Cancer in a Chinese Population

BackgroundEsophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis.MethodsWe conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method.ResultsWhen the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.58–0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.59–0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed.Conclusion TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.