Comparison Of Genotype Frequencies Research Articles

IL-10 polymorphism genotypes, haplotypes, and diplotypes are associated with colorectal cancer predisposition and outcome in Tunisian population

Background and aimAs the presence of single nucleotide polymorphisms (SNPs) in the interleukin (IL)-10 gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (−1082A/G (rs1800896) and −592A/C (rs1800872)) located in the promoter region of IL-10 gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians. MethodsIL-10 gene SNPs were analyzed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP. ResultsFor the IL-10 -1082A/G SNP, the comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA + AG: OR [95%CI] = 0.44 [0.21–0.93], p = 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA + GG) and high susceptibility (OR [95%CI] = 1.65 [1.02–2.63], p = 0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI] = 0.18 [0.04–0.72], p = 0 0.01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI] = 5.16 [1.31–23.26], p = 0.02). Furthermore, the codominant model (AG vs. AA + GG) doubled the risk of rectum cancer (OR [95%CI] = 1.98 [1.07–3.70], p = 0.03). For the IL-10 -592A/C SNP, the codominant model (AC vs. AA + CC) has a protective effect against the development of CRC (OR [95%CI] = 0.59 [0.36–0.94], p = 0.03). The IL-10 gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (−1082G and −592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI] = 0.51 [0.32–0.80], p = 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI] = 0.35 [0.14–0.85], p = 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p = 0.01). This association was also observed in the colon cancer subgroup (Log-rank: p = 0.001). ConclusionOur findings provide preliminary indications that the −1082A/G and −592/AC SNPs within the IL-10 gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.

Preliminary study: nutrigenomics analysis results of COVID-19 survivors

BackgroundNumerous attempts have been made at both prevention and treatment of COVID-19. Specific genotypes carry a risk of causing clinical symptoms that can be beneficial or detrimental. We performed nutrigenomics testing on COVID-19 survivors who were on ventilators during their treatment and mild COVID-19 survivors who did not require ventilators to determine the risk of genetic variation through nutrigenomic testing regarding COVID-19 incidence. DNA was isolated from saliva and genotyped for genetic markers using a commercially available nutrigenomics test. We compared genotype frequencies between those with severe symptoms (cases) and those with mild symptoms (controls).ResultSequencing results showed that the distribution from pattern of the Sankey diagram included an ultra risk category in the control group, but not in the case group. None of the subjects in the case group were in the ultra risk category for resilience. A descriptive pattern of risk-level distribution was observed in both the control and case groups. One subject in the ultra risk category was in the control group, indicating a lower risk factor for severe COVID-19.ConclusionFrom this study, a uniqueness begins to emerge, revealing the discovery of ultra-category patterns in the endurance of the control group. The vitamin E risk deficiency is significantly higher in the severe COVID-19 group compared to the mild group, categorized as "typical."

The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals.

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.

Identification of a Predictive Model for Schizophrenia Based on SNPs in a Chinese Population.

Schizophrenia is a devastating mental disease with high heritability. A growing number of susceptibility genes associated with schizophrenia, as well as their corresponding SNPs loci, have been revealed by genome-wide association studies. However, using SNPs as predictors of disease and diagnosis remains difficult. Here, we aimed to uncover susceptibility SNPs in a Chinese population and to construct a prediction model for schizophrenia. A total of 210 participants, including 70 patients with schizophrenia, 70 patients with bipolar disorder, and 70 healthy controls, were enrolled in this study. We estimated 14 SNPs using published risk loci of schizophrenia, and used these SNPs to build a model for predicting schizophrenia via comparison of genotype frequencies and regression. We evaluated the efficacy of the diagnostic model in schizophrenia and control patients using ROC curves and then used the 70 patients with bipolar disorder to evaluate the model's differential diagnostic efficacy. 5 SNPs were selected to construct the model: rs148415900, rs71428218, rs4666990, rs112222723 and rs1716180. Correlation analysis results suggested that, compared with the risk SNP of 0, the risk SNP of 3 was associated with an increased risk of schizophrenia (OR = 13.00, 95% CI: 2.35-71.84, p = 0.003). The ROC-AUC of this prediction model for schizophrenia was 0.719 (95% CI: 0.634-0.804), with the greatest sensitivity and specificity being 60% and 80%, respectively. The ROC-AUC of the model in distinguishing between schizophrenia and bipolar disorder was 0.591 (95% CI: 0.497-0.686), with the greatest sensitivity and specificity being 60% and 55.7%, respectively. The SNP risk score prediction model had good performance in predicting schizophrenia. To the best of our knowledge, previous studies have not applied SNP-based models to differentiate between cases of schizophrenia and other mental illnesses. It could have several potential clinical applications, including shaping disease diagnosis, treatment, and outcomes.

Cytochrome P450 2C19*2 Genetic Polymorphism in Patients with Acute Coronary Syndrome

Objectives: The study aimed to investigate the association between CP2C19*2 loss of function polymorphism and acute coronary syndrome (ACS) patients receiving Clopidogrel. It compared genotype frequencies of heterozygous GA, homozygous GG, and homozygous AA between ACS patients and healthy controls. The study assessed the statistical significance of the association in the Pakistani cohort. It contributed to understanding the role of genetic polymorphisms in response to Clopidogrel therapy in ACS patients and provided insights into the need for pharmacogenomics testing for patients with CAD, particularly in the Asian population, who are poor metabolizers and require long-term Clopidogrel therapy.&#x0D; Methodology: COHORT Study.&#x0D; Results: The study found no statistically significant association between the CYP2C19*2 loss of function polymorphism and acute coronary syndrome (ACS) in the Pakistani cohort. The frequency of the CP2C19*2 heterozygous GA genotype was 38.3% in ACS patients and 29.5% in control subjects, while the homozygous GG genotype was 58.7% in patients and 59.0% in controls. The homozygous AA genotype was 3.4% in patients and 11.4% in controls.&#x0D; The genotype frequency analysis showed that the wild type GG genotype was lower in patients (58.7%) compared to controls (59.0%), while the mutant AA genotype was also lower in patients (3.4%) compared to controls (11.4%). The heterozygous GA genotype was higher in patients (38.3%) compared to controls (29.5%).&#x0D; The population studied was in Hardy Weinberg equilibrium, with a frequency of mutant allele A at 0.26 and wild type allele G at 0.73.&#x0D; Conclusion: The study concludes that the CYP2C19*2 loss of function polymorphism is not associated with acute coronary syndrome (ACS) in the Pakistani cohort. The distribution of the CP2C19*2 genetic polymorphism was not statistically significant between ACS patients and healthy controls.&#x0D; The genotype frequency analysis showed no significant differences in the distribution of the heterozygous GA, homozygous GG, and homozygous AA genotypes between the patient and control groups.&#x0D; The population studied was in Hardy Weinberg equilibrium, with a frequency of mutant allele A at 0.26 and wild type allele G at 0.73.

Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis.

Objectives: Micro ribonucleic acids (miRNAs) are noncoding RNAs, recently implicated as potential biomarkers or therapeutic targets for autoimmune diseases such as rheumatoid arthritis (RA). The aim of this study is to assess the role of miRNA Let-7 in the plasma of RA. Materials and methods: Trained medical staff already enrolled for the study collected blood samples from healthy controls (N = 42) and RA patients (N = 44). In the laboratory, these samples were centrifuged at 2000 rpm for 8 minutes to separate serum from the sample, which was then transferred to a plain vial. Until transport to the genetic lab, samples were stored at -20°C Deoxyribonucleic acid (DNA) was isolated using a standard protocol cohort of controls and patient blood samples. Quantification of DNA was conducted using ultraviolet (UV) spectroscopy, and DNA quality was assessed on 0.8% agarose gel. A comparison of genotype frequencies in the different study groups was performed using the Chi-squared test, while a comparison of allelic frequencies was conducted using Fisher's exact test. Results: Variations of alleles, such as 16539423 (G>T), 16539433 (T>G), and 16539629 (A>T) were found only in RA patients. On the other hand, 16539617 (T>A), 16539622 (G>T), and 16539624 (T>C) were found only in control cases. Five sequences (three RA variants and two control variants) with minimal alignment were compared to the wild-type sequence. We found that the sequence modification of pre-miRNA 16539623 del G was significantly higher and had a risk allele in the study group [odds ratio (OR) = 3.29]. Conclusion: Rheumatoid arthritis (RA) is an autoimmune disorder that presents with a variety of clinical manifestations. Genetic factors possibly account for about 60% of disease susceptibility and expression, thus playing a very important role in disease pathogenesis. How to cite this article: Gauri LA, Liyakat N, Dadhich D, et al. Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis. J Assoc Physicians India 2023;71(11):50-52.

Platelet Glycoprotein Receptor Ia-C807T and IIIa-PlA1/PlA2 Genetic Polymorphisms Are Associated With Enhanced Platelet Function in Women With Recurrent Miscarriages.

Thrombophilic genetic polymorphisms of the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa) have been associated with an increased risk of recurrent miscarriages. The aim of this study was to investigate the association of genetic polymorphisms GpIa-C807T and GpIIIa-T1565C-PlA1/PlA2 with platelet function in women with unexplained spontaneous recurrent miscarriages. This cross-sectional study comprised 196 unrelated nulliparous Greek women with a history of unexplained recurrent miscarriages. Patients were genotyped for the presence of the GpIa-C807T (rs1126643) and GpIIIa-T1565C-PlA1/PlA2 (rs5918) genetic polymorphisms by pyrosequencing, and the collagen/epinephrine closure time (COL/EPI CT) of the subjects was assessed using the platelet function analyzer (PFA)-100. In the total population of women with recurrent miscarriages, the COL/EPI CT ranged from 70 to 160 seconds (median: 122 seconds, interquartile range (IQR): 102.3-138 seconds). In comparison with the double homozygotes CC/PlA1PlA1 that had the most prolonged CT (mean: 131.9 ± 17.5 seconds), the COL/EPI CT was statistically significantly shorter for the GpIa-807T single carriers (mean: 120.3 ± 20.9 seconds) (p=0.011) (absolute difference: 11.6 seconds, 95% confidence interval (CI): 21.2 to -2.0 seconds;relative difference: -9%, 95% CI: -16% to -2%), and the GpIIIa-PlA2 single carriers also displayed a trend for shorter COL/EPI CT (mean:121.3 ± 23.7 seconds) (p=0.141) (absolute difference: -10.6 seconds, relative difference: -8%), whereas the combined carriers of the GpIa-807T and the GpIIIa-PlA2 alleles exhibited the shortest COL/EPI CT (mean: 104.1 ± 19.7 seconds) (absolute difference: -27.7 seconds, 95% CI: -39.1 to -16.3 seconds; relative difference: -21%, 95% CI: -30% to -12%) (p<0.001). In comparing genotype frequencies in the lower half with those in the upper half of the COL/EPI CT range, the GpIa-807T and the GpIIIa-PlA2 single carriers were associated with higher odds of COL/EPI CT < 122 seconds (odds ratio (OR)=3.4, 95% CI: 1.5 to 7.5, p=0.002, and OR=2.6, 95% CI: 1.0 to 7.2, p=0.053, respectively). The association was strongest for the combined carriers with OR of 15.0 (95% CI: 5.2 to 43.2, p<0.001) for COL/EPI CT below the medianand OR of 35.5 (95% CI: 4.4 to 284.5, p<0.001) for COL/EPI CT < 100 seconds. The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly the combined carriers of the risk variants are associated with enhanced platelet reactivity expressed via shorter COL/EPI CT. These findings provide further evidence for the role of platelet-associated genetic thrombophilia in the pathogenesis of recurrent miscarriages and promotethe analysis of platelet function as a diagnostic tool in the evaluation of this disorder.

Abstract 2247: Evaluation of multidrug resistant genes among breast cancer patients in Ghana

Abstract Background: Breast cancer (BC) is a leading cause of cancer death in Ghana and around the world. Ghanaian women are diagnosed at younger ages with the more aggressive Triple Negative BC (TNBC) subtype where West African ancestry is associated with advanced BC diagnosis and higher mortality rates compared to age-matched women of European ancestry. Genomic comparisons of BC tumors from women of African and European ancestry show differences in frequencies of single nucleotide polymorphisms (SNP) and copy number variations. These differences may contribute to disparities in disease and treatment outcomes observed in women of African ancestry. Chemotherapy plays a major role in treatment of recurrent and metastatic BC. Long-term BC survival remains poor especially in Africa due to multidrug resistance (MDR). MDR has been associated with binding cassette (ABC) protein transporters. ABCB1, ABCC1 and ABCG2 are ABC transporter genes that code for proteins involved in drug efflux. We hypothesize that SNPs in ABC transporter genes may alter their physiological protective role and increase risk of MDR, treatment failure and death among BC patients. Preliminary dataWe explored gene expression profiles of ABCB1, ABCC1 and ABCG2 in an African ancestry-enriched subset of women with TNBC (ICSBCS cohort: Ghanaian n = 6, African American (AA) n = 9, Ethiopian n = 11). Preliminary data showed significantly higher expression of ABCC1 among Ghanaian and AA patients compared to Ethiopians, and a significant positive correlation with African ancestry. ABCB1 and ABCG2 showed lower expression in all three groups (ns).To study the relationship between ABC transporter gene SNPs and MDR, we have collected data over a 3-year period (2019-2021) from the Oncology Department of the Komfo Anokye Teaching Hospital in Ghana. The overall prevalence of BC recurrence was 3.4% (CI = 2.5 - 4.7%), and prevalence of metastatic BC was 47.6% (CI = 44.6 - 50.6%). Methodology: SNPs in ABC transporter genes will be obtained from 150 consented female BC patients who have undergone chemotherapy. We will compare genotype frequencies among patients with disease recurrence and/or metastasis (n = 100) to those with no disease recurrence or metastasis (n = 50). Single-plex genotyping of the ABC gene SNPs will be completed using a real-time PCR allelic discrimination assay. Conclusion: ABCC1 has been established to be associated with African ancestry. Determining the association of ABC gene SNPs and MDR among Ghanaian BC patients will provide further information on allelic variants and their effects on BC treatment outcomes. Citation Format: Gloria Agyekum Boaitey, Rachel Martini, Melissa B. Davis, Lisa Newman, Brian Stonaker, Linda Ahenkorah Fondjo, Christian Obirikorang, Ernest Osei Bonsu, Ernest Adjei, Ishmael Kyei, Mavis Bobie Ansah, Mahteme Bekele, Timothy Chu, Nicolas Robine. Evaluation of multidrug resistant genes among breast cancer patients in Ghana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2247.

Rapid evolution of a coastal marsh ecosystem engineer in response to global change

There is increasing evidence that global change can alter ecosystems by eliciting rapid evolution of foundational plants capable of shaping vital attributes and processes. Here we describe results of a field-scale exposure experiment and multilocus assays illustrating that elevated CO2 (eCO2) and nitrogen (N) enrichment can result in rapid shifts in genetic and genotypic variation in Phragmites australis, an ecologically dominant plant that acts as an ecosystem engineer in coastal marshes worldwide. Compared to control treatments, genotypic diversity declined over three years of exposure, especially to N enrichment. The magnitude of loss also increased over time under conditions of N enrichment. Comparisons of genotype frequencies revealed that proportional abundances shifted with exposure to eCO2 and N in a manner consistent with expected responses to selection. Comparisons also revealed evidence of tradeoffs that constrained exposure responses, where any particular genotype responded favorably to one factor rather than to different factors or to combinations of factors. These findings challenge the prevailing view that plant-mediated ecosystem outcomes of global change are governed primarily by differences in species responses to shifting environmental pressures and highlight the value of accounting for organismal evolution in predictive models to improve forecasts of ecosystem responses to global change.

Circulating Genotypes of Hepatitis C Virus in Italian Patients before and after the Application of Wider Access Criteria to HCV Treatment

Aims: The aims of this study were to report a description of the HCV genotype distribution in adult Italians and non-Italians subjects tested in the Microbiology and Virology Unit of the Padova University Hospital from January 2016 (after about one year from the availability of DAAs) to December 2018 and to compare genotype frequencies in the 12-month period before and after the application of the wider access criteria to HCV treatment. Background: Hepatitis C virus (HCV) infection is a major health problem, but the availability of direct-acting antivirals (DAAs) has dramatically changed HCV disease natural history because these drugs have excellent tolerability and they can eliminate the virus in almost all treated patients. Objective: The objective was to describe the circulating HCV genotypes in high-income countries in order to help health authorities in the future organization of DAAs treatment strategies; this aspect is not limited to drug prescription, but it also includes the identification of infected individuals who are undiagnosed, which is the limiting step to achieve the HCV elimination goal. Methods: Adult patients who had HCV genotype performed from 01/01/16 to 31/12/18 in the Microbiology and Virology Unit of the Padova University Hospital were included in the study: the two 12-month periods were April 2016-March 2017 (before period, BEF) and April 2017-March 2018 (after period, AFT). Results: Italians were 2168 (91.2%) and non-Italians were 208 (8.8%). Italians median age was 55 years, and females were older. Italians had a lower genotype 1 (p=0.0012) and higher genotype 2 frequencies (p&lt;0.0001) with respect to non-Italians. Most patients aged 38-67 years: Italians were more represented in class age 48-57 years (p=0.0138), 68-77 years (p=0.001) and ≥78 years (p&lt;0.0001); subjects with genotype 3 were the youngest and those with genotype 2 the oldest. Italian patients typed in the AFT and BEF were comparable; only a lower frequency of genotype 1 males and younger age in genotype 3 were found in AFT. Conclusion: Italians were older with respect to non-Italians, which implies that a different age based screening program could be applied. Italian genotype 3 subjects represent a cohort to focus on for the risk of therapeutic failure. Patients tested after the extended criteria for HCV treatment were very similar to those tested before, suggesting that HCV burden in Italians is higher than expected.

Association of single nucleotide polymorphic variants of the &lt;i&gt;NOS1AP&lt;/i&gt; gene with QT interval duration

Highlights. The association of single nucleotide polymorphic variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval was found in men of the Siberian population.Aim. To study the association of single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval.Methods. The study sample of men (1353 people) aged 25–69 years was formed from the DNA bank of participants in the international HAPIEE project and screening of young people 25–44 years old, residents of Novosibirsk. From each age subgroup (25–29, 30–34, …, 65–69 years old), about 10–15% of men with the shortest, average and longest QT interval were selected and the corresponding groups were formed. Genotyping of rs4657139 was carried out using PCR with RFLP (polymerase chain reaction followed by restriction fragment length polymorphism analysis). Genotyping rs12143842 – using RT-PCR (real-time polymerase chain reaction).Results. At the age of over 50 years, the CC genotype rs12143842 was detected in 66.1% of men in the group with a short and average QT interval and in 50.6% in the group with a long QT interval, while the TT genotype prevailed in the group with a long QT interval, 10, 8% of cases (odds ratio (OR) = 3.345, 95% confidence interval (CI) 1.149–9.739, p = 0.02). The homozygous TT genotype rs4657139 was more common in the long QT group, in 20.1% of cases, while the AA and AT genotypes predominated in the short, average QT groups (p = 0.041). A similar trend persists when separating by age in people over 50 years of age (p = 0.031) and when comparing genotype frequencies in the long and average QT groups in the model TT vs AA + AT &amp; long QT vs short + average QT (p = 0.003).Conclusion. Single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene are associated with the duration of the QT interval in male residents of Novosibirsk.

Association of interleukin-17A gene promoter polymorphism with the susceptibility to generalized chronic periodontitis in an Iranian population

Chronic periodontitis (CP) is characterized by an immune response, leading to the destruction of periodontal supporting tissue. The effect of inflammatory and genetic factors on periodontitis has been evaluated previously. The interleukin (IL-17) as an inflammation regulator seems to play a critical role in periodontitis pathogenesis. Here, in the current study, we aimed to investigate the association of -197 G > A (rs2275913) IL-17 gene promoter polymorphism with generalized severe CP in an Iranian population. In this case-control study, a total of 54 patients with periodontitis and 118 normals were enrolled. The polymerase chain reaction-restriction fragment length polymorphism technique was applied to detect IL-17 promoter rs2275913 genotypes in association with the susceptibility to severe CP. Chi-square test or Fisher's exact test was employed to compare genotype frequencies between groups. P < 0.05 were considered statistically significant. The distribution of genotypes and alleles was in Hardy-Weinberg equilibrium. Although no significant association was observed between the risk of periodontitis and genotype frequencies under any of the inheritance models, the GG genotype was higher in healthy controls, while the AG genotype was more frequently observed in patients under the codominant model ([odd ratio [OR] = 2.14, 95% confidence interval (CI) (1.01-4.53), P = 0.13]). The frequency of AG-AA genotype was higher in patients under dominant inheritance model ([OR = 1.92, 95% CI (0.94-3.93), P = 0.068]), while GG-AA and AG genotypes were higher in healthy controls under over dominant model (OR = 0.1.95, 95% CI [0.98-3.86], P = 0.055). The results of this study showed that the presence of allele A and AG genotypes could be considered possible factors in increasing the risk of developing CP, although the differences of allele and genotype frequencies were remarkable but not statistically significant between the two groups.

Differences in the genotype frequencies of genes related to blood pressure regulation - a comparative study between South-West Europe and Peri-equatorial Africa.

Since the emergence of the genus Homo, hominids have occupied a wide variety of environments, facing different selective pressures. The aim this study is to compare genotype frequencies between South-West Europe and Peri-equatorial Africa in genes potentially modulators of blood pressure. The analyzed sample consisted of 325 individuals from Portugal and 226 individuals from Africa (48 from Mozambique and 178 from São Tomé and Príncipe). The following genetic variants were analyzed: intron 4 VNTR in eNOS, rs1050829 in G6PD, -3.7kb α-thalassemic deletion in HBA, rs1800457 in CYB5R3, Hp 1/2 genotype/phenotype in Hp and intron 16 I/D in ACE. Frequencies of genotypes with the 4a allele in eNOS (p<0.001), the G allele in G6PD (p<0.001), the α-3.7 kb in HBA (p <0.001), the C allele in the CYB5R3 (p<0.001) were higher in Peri-equatorial Africa. The Hp 1.1 genotype of Hp has a higher frequency in Peri-equatorial Africa (p=0.002). ACE shows no significant differences. Results show differences in five genetic variants. Conditions of extreme heat and humidity, characteristic of Peri-equatorial Africa, have been associated with increased sodium loss. This study suggests that selected compensatory mechanisms printed in the genome, are nowadays risk factors for hypertension in Peri-equatorial Africa.

Evaluating the role of inherited thrombophilia genes with recurrent pregnancy loss among Egyptian couples

AimThromboembolic disorders including venous or arterial thrombosis within pregnancy are an important reason for maternal morbidity and mortality. Early detection of pregnant women with thromboembolic disorders asymptomatic is clinically important to decrease incidence of adverse pregnancy outcomes. Aim of this study is to assess frequency of three thrombophilic mutations [Factor V Leiden (FVL), Prothrombin G20210A (PT) and Methylenetetrahydrofolate reductase (MTHFR) A1298C] among Egyptian couples with RPL. Methods115 couples with recurrent pregnancy loss were enrolled in the study. To compare genotype frequency, we have selected 115 healthy fertile couples without history of RPL as control group. Genomic DNA was evaluated using Real time PCR to determine the genotype frequency. ResultsAllele frequencies of PT and MTHFR A1289C were similar between cases and controls. A allele in FVL G1619A among RPL patients was 15.7% vs. 4.3% among controls, P value; 0.001, OR: 4.0 (95% CI; 1.9–8.4). The incidence of multiple thrombophilic mutations among case group versus control group was as follows; In RPL patients 8.7% vs.1.7%; p 0.018 OR: 3.6 (95%CI; 1.3–9.3). Individual Male partners 16.5% vs.5.2%; p 0.006; OR 3.6 (95%CI; 1.3–9.3) and for the couples 25.2% vs.11.3%; p 0.006 OR4.3 (95%CI; 1. 8–9.9). ConclusionFVL mutation is significantly associated with RPL in contrast to MTHFR A1298C and PT G2010A. The presences of more than one thrombophilic defects (multiple thrombophilic mutations) within the same individual as well as consanguinity are significantly associated with RPL couples.

The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

P1613INFLUENCE OF GENETIC POLYMORPHISM IN MMPS AND TIMPS ON ALLOGRAFT OUTCOME IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Renal transplantation (RT) is currently the most effective replacement therapy and believed as a boon for patients with end-stage renal disease (ESRD). Allograft rejection remains to be one of the crucial impediments in successful renal transplantation. Matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMPs) play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The study of MMPs and TIMPs in transplant rejection may also lead to novel approaches in the therapy of rejection processes. To investigate the association of functional polymorphisms in MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G); MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A); TIMP1(+536 C/T) and TIMP3(-1298 C/T gene with risk of allograft rejection in renal transplant recipients of North India. Method A total of two hundred live related renal transplant donors and recipients pairs blood sample was collected and were genotyped for MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G); MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A); TIMP1(+536 C/T) and TIMP3(-1298 C/T) gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) methodology. All two hundred renal transplant recipients were categorized into 162 non-rejecters and 32 rejecters and were analyzed further. All the statistical analysis was done using SPSS software. Results The genotype frequencies of MMP1 (-1607 1G/2G) [2G/2G; odds ratio (OR) = 2.97, 95% confidence intervals (95% CI) = 1.69-5.20, P ≤ 0.05]; MMP9 (Q279R) [RQ; odds ratio (OR) = 0.47, 95% confidence intervals (95% CI) = 0.25-0.99, P = 0.02 &amp; QQ; odds ratio (OR) = 0.49, 95% confidence intervals (95% CI) = 0.25-0.94, P = 0.03]; MMP9 (P574R) [PR; odds ratio (OR) = 2.70, 95% confidence intervals (95% CI) = 1.77-4.13, P ≤ 0.05 &amp; RR; odds ratio (OR) = 2.70, 95% confidence intervals (95% CI) = 1.09-6.71, P = 0.03]; TIMP1(+536 C/T) [CT; odds ratio (OR) = 15.41, 95% confidence intervals (95% CI) = 9.12-26.05, P ≤ 0.05 &amp; TT; odds ratio (OR) = 7.01, 95% confidence intervals (95% CI) = 3.39-14.49, P ≤ 0.05] and TIMP3(-1298 C/T) [CT; odds ratio (OR) = 0.31, 95% confidence intervals (95% CI) = 0.19-0.50, P ≤ 0.05] was significantly associated with allograft rejection. On comparison of genotypic frequencies for MMP-1, MMP-3, MMP-9, TIMP1 and TIMP3 gene polymorphisms between rejecters and non-rejecters no significant difference was found while comparing genotypic frequencies of non-rejecters with donors a significant association was observed in MMP1 (-1607 1G/2G) [P ≤ 0.05]; MMP9 (Q279R) [P = 0.02]; MMP9 (P574R) [P ≤ 0.05]; TIMP1 [P ≤ 0.05] and TIMP 3 [P ≤ 0.05] respectively. Therefore, MMP1 (-1607 1G/2G), MMP9 (Q279R), MMP9 (P574R), TIMP1 and TIMP3 demonstrated significantly reduced risk for allograft rejection. MMP1 (-1607 1G/2G) [P ≤ 0.02]; MMP9 (P574R) [P ≤ 0.05]; TIMP1 [P ≤ 0.05] and TIMP3 [P =0.01] was also found significantly associated on comparison between rejecters and donors. Conclusion Mutant genotypes/ alleles for MMP1 (-1607 1G/2G); MMP9 (Q279R); MMP9 (P574R); TIMP1 (+536 C/T) and TIMP3 (-1298 C/T) are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.

Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis.

The development of recurrent aphthous stomatitis (RAS), inflammatory disease of oral mucosa, is influenced by both environmental and genetic factors. The aim of this study was to investigate polymorphisms located in seven genes coding different types of matrix metalloproteinases (MMPs)-collagenases (MMP1, MMP8, and MMP13), gelatinases (MMP2 and MMP9), stromelysin (MMP3), and membrane-type metalloproteinase (MMP16) in patients with RAS and healthy controls. Totally, 223 subjects were included in this case-control study and their detailed anamnestic, clinical, and laboratory parameters were recorded. Seventy-seven patients with RAS and 146 controls were genotyped for seventeen polymorphisms in the MMPs genes using the real-time polymerase chain reaction (PCR) or PCR with restriction analysis. Allele, genotype, and haplotype frequencies of the studied polymorphisms between RAS patients and controls were similar, except for allele distributions of MMP1 rs1144393, MMP9 rs3918242, and MMP16 rs10429371, which were different between patients with RAS and healthy controls (P=.023, P=.049 and P=.025, all Pcorr >0.05, respectively). Moreover, the comparison of genotype frequencies (TT vs CC+CT) of the MMP16 rs10429371 variant showed a marginally significant difference between RAS patients and controls (P=.05, Pcorr >0.05, OR=1.68, 95% CI=0.95-2.98). No significant relationship between investigated polymorphisms in seven MMPs genes and RAS development in the Czech population was observed in this study.

Genetic Markers at ANRIL, FTO and 2q36.3 Locus in Czech Patients Undergoing Coronary Artery Bypass Graft Surgery.

Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95 % CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.

Genetic Variants on SCN5A, KCNQ1, and KCNH2 in Patients with Ventricular Arrhythmias during Acute Myocardial Infarction in a Chinese Population

Objective: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. About half of sudden deaths from AMI are mainly because of malignant ventricular arrhythmias (VA) after AMI. The sodium channel gene SCN5A and potassium channel genes KCNQ1 and KCNH2 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS). A few studies reported the association of SCN5A variant with ventricular tachycardia (VT)/ventricular fibrillation (VF) complicating AMI. However, little is known about the role of KCNQ1 and KCNH2 in AMI with VA (AMI_VA). This study focuses on investigating the potential variants on SCN5A, KCNQ1, and KCNH2 contributing to AMI with VA in a Chinese population. Materials and Methods: In total, 139 patients with AMI_VA, and 337 patients with AMI only, were included. Thirty exonic sites were selected to be screened. Sanger sequencing was used to detect variants. A subsequent association study was also performed between AMI_VA and AMI. Results: Twelve variants [5 on KCNH2(NM_000238.3), 3 on KCNQ1(NM_000218.2), and 4 on SCN5A(NM_198056.2)] were identified in AMI_VA patients. Only 5 (KCNH2: c.2690A>C; KCNQ1: c.1927G>A, c.1343delC; SCN5A: c.1673A>G, c.3578G>A) of them are missense variants. Two (KCNQ1: c.1343delC and SCN5A: c.3578G>A) of the missense variants were predicted to be clinically pathogenic. All these variants were further genotyped in an AMI without VA group. The association study identified a statistically significant difference in genotype frequency of KCNH2: c.1539C>T and KCNH2: c.1467C>T between the AMI and AMI_VA groups. Moreover, 2 rare variants (KCNQ1: c.1944C>T and SCN5A: c.3621C>T) showed an elevated allelic frequency (more than 1.5-fold) in the AMI_VA group when compared to the AMI group. Conclusion: Twelve variants (predicting from benign/VUS to pathogenic) were identified on KCNH2, KCNQ1, and SCN5A in patients with AMI_VA. Genotype frequency comparison between AMI_VA and AMI identified 2 significant common variants on KCNH2. Meanwhile, the allelic frequency of 2 rare variants on KCNQ1 and SCN5A, respectively, were identified to be enriched in AMI_VA, although there was no statistical significance. The present study suggests that the ion-channel genes KCNH2, KCNQ1, and SCN5A may contribute to the pathogenesis of VA during AMI.