Additive Model Of Inheritance Research Articles

PAGER: A novel genotype encoding strategy for modeling deviations from additivity in complex trait association studies

BackgroundThe additive model of inheritance assumes that heterozygotes (Aa) are exactly intermediate in respect to homozygotes (AA and aa). While this model is commonly used in single-locus genetic association studies, significant deviations from additivity are well-documented and contribute to phenotypic variance across many traits and systems. This assumption can introduce type I and type II errors by overestimating or underestimating the effects of variants that deviate from additivity. Alternative genotype encoding strategies have been explored to account for different inheritance patterns, but they often incur significant computational or methodological costs. To address these challenges, we introduce PAGER (Phenotype Adjusted Genotype Encoding and Ranking), an efficient pre-processing method that encodes each genetic variant based on normalized mean phenotypic differences between diallelic genotype classes (AA, Aa, and aa). This approach more accurately reflects each variant’s true inheritance model, improving model precision while minimizing the costs associated with alternative encoding strategies.ResultsThrough extensive benchmarking on SNPs simulated with both binary and continuous phenotypes, we demonstrate that PAGER accurately represents various inheritance patterns (including additive, dominant, recessive, and heterosis), achieves levels of statistical power that meet or exceed other encoding strategies, and attains computation speeds up to 55 times faster than a similar method, EDGE. We also apply PAGER to publicly available real-world data and identify a novel, relevant putative QTL associated with body mass index in rats (Rattus norvegicus) that is not detected with the additive model.ConclusionsOverall, we show that PAGER is an efficient genotype encoding approach that can uncover sources of missing heritability and reveal novel insights in the study of complex traits while incurring minimal costs.

Association of the vitamin D metabolism gene polymorphism with the severity of coronary lesions assessed by SYNTAX score

This study aimed to determine the association of vitamin D serum blood levels and vitamin D gene polymorphism with the severity of coronary lesions in patients with stable coronary artery disease (CAD). Material and methods. 260 patients with stable CAD (average age was 58 years) were examined in the presented research. All patients were divided into two groups according to the SYNTAX score: low-risk patients with SYNTAX score ≤ 31 (n = 224) and high-risk patients with SYNTAX score > 31 (n = 36). For enzyme-linked immunosorbent assay and genetic analysis, peripheral blood was collected from the cubital vein into vacuum tubes containing coagulation activator and K3-EDTA, respectively. Serum blood level of 25-hydroxyvitamin D (DiaSource Diagnostics, Belgium) and 1,25-dihydroxyvitamin D (Immunodiagnostic Systems, Great Britain) were determined by enzyme-linked immunosorbent assay according to the manufacturers’ protocols. Genomic DNA was isolated by phenol-chloroform extraction method from whole blood. The quality and quantity of isolated DNA were assessed using NanoDrop spectrophotometer (Thermo Fisher Scientific, USA). Five polymorphic variants in the VDR (rs2228570 and rs73123) and GC (rs7041, rs1155563 and rs2298849) genes were selected for analysis. Genotyping was performed by real-time PCR in a 96-well plate with fluorescently labeled TaqMan probes. The quality of PCR was controlled by repeated genotyping of 10 % of the analyzed samples. Results. We found no statistically significant differences in serum blood level of the studied markers in patients from low-risk and high-risk groups. One polymorphic variant in the GC gene associated with the multiple coronary lesions (rs2298849) (odds ratio 2.26, 95 % confidence interval 1.28–3.99, p = 0.006) according to an additive inheritance model was identified. In addition, we determined the association between low serum blood level of 1,25-dihydroxyvitamin D in patients with CAD with multiple lesions of the coronary vascular system with A/A – A/G genotypes of the rs2228570 polymorphism in the VDR gene, A/A genotype of the rs7041 polymorphism and A/A genotype of the rs2298849 polymorphism in the GC gene. Conclusions. Allelic variants in the vitamin D metabolism genes are associated with the degree of coronary artery lesions assessed by the SYNTAX score in patients with stable CAD. Also, serum blood level of the active form of vitamin D (1,25-dihydroxyvitamin D) is less in carriers of homozygous genotypes for the major alleles of the VDR and GC genes.

Nonadditive Effects of Common Genetic Variants Have a Negligent Contribution to Cancer Heritability.

Contribution of dominance effects to cancer heritability is unknown. We leveraged existing genome-wide association data for seven cancers to estimate the contribution of dominance effects to the heritability of individual cancer types. We estimated the proportion of phenotypic variation caused by dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, nonmelanoma skin, ovarian, and prostate) in a total of 166,772 cases and 284,824 controls. We observed no evidence of a meaningful contribution of dominance effects to cancer heritability. By contrast, additive effects ranged between 0.11 and 0.34. In line with studies of other human traits, the dominance effects of common genetic variants play a minimal role in cancer etiology. These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.

CLINICAL COURSE OF OBESITY-ASSOCIATED ASTHMA DEPENDING ON THE GLN27GLU POLYMORPHIC VARIANT OF THE β2-ADRENORECEPTOR GENE, TAKING INTO ACCOUNT THE AGE OF ONSET

Introduction. Studies have shown that bronchial asthma (BA) associated with obesity has a more severe course, lower control, more frequent cases of low efficacy of basic treatment, and exacerbations. Two phenotypes have been distinguished in BA-obesity comorbidity based on age of onset: early atopic and late non-atopic. It is known that genetic factors associated with β2-adrenoceptor (AR) genes are important in the development of both asthma and obesity.
 The purpose of the study aimed to analyze the association of the Gln27Glu polymorphism of the β2-adrenoceptor gene with the severity of the course of bronchial asthma with obesity, taking into account the age of its onset.
 Research material and methods. 195 asthma patients with obesity consented for the study participation were examined. The control group consisted of 95 practically healthy people. Patients were divided into two clinical groups depending on the age of onset of BA: the first group included 100 patients with an early onset, the second group - 95 patients with a late onset. The diagnosis and treatment of asthma followed the guidelines of the Global Initiative for Asthma (2016) and its updated versions. The study was approved by the Bioethics Commission of the Educational and Scientific Medical Institute of Sumy State University. Determination of the Gln27Glu polymorphism of the β2-AR gene (rs1042714) was performed using the polymerase chain reaction with the subsequent analysis of restriction fragments. Statistical analysis of the obtained results was carried out using the SPSS-17 program. Pearson's chi-squared test was used to compare genotype distributions between experimental groups. To determine the risk of BA and obesity, odds ratios and 95% confidence intervals were calculated for dominant, recessive, superdominant, and additive models of inheritance. Their relevance was assessed using the Akaike information criterion. All tests were two-sided, and values p < 0.05 were considered statistically significant.
 Research results. The frequency of Gln/Gln, Gln/Glu and Glu/Glu genotypes according to the Gln27Glu polymorphism of the β2-AR gene in patients with early-onset obesity-associated asthma was 70.0; 25.0; 5.0% with a mild course and 55.0; 36.2; 8.8% with severe (χ2 = 1.49; p = 0.473); and with a late debut - 50.0; 43.8; 6.2% with mild and 54.0%; 31.7; 14.3%, respectively, with severe (χ2 = 2.10; p = 0.350). Despite the absence of a probable difference in the distribution of genotypes depending on the severity of the course, it was found that the frequency of homozygotes for the minor allele was 1.8 times higher in patients with a severe course of early BA and 2.3 times higher in late BA compared to that in patients with mild BA course.
 The risk of early-onset BA with obesity and a severe course showed no association in all models of inheritance, and in patients with late-onset BA, there was a 1.66-fold increase (95% CI (1.03 – 2.72), p = 0.04) in the additive inheritance model (p = 0.04).
 Conclusions. There are no statistically significant differences in the distribution of genotypes according to the Gln27Glu polymorphism of the β2-AR gene depending on the severity of the course of early and late BA with obesity. The risk of developing a severe course of early BA did not depend on the Gln27Glu polymorphism of the β2-AR gene, and late BA increased by 1.66 times in the additive model of inheritance.

Abstract A109: Novel germline genetic variants in pseudogenes associated with overall survival in advanced stage ovarian cancer treated with carboplatin, paclitaxel, and bevacizumab: Results from the ROSiA trial

Abstract A109: Novel germline genetic variants in pseudogenes associated with overall survival in advanced stage ovarian cancer treated with carboplatin, paclitaxel, and bevacizumab: Results from the ROSiA trial

Association of the C allele of rs479200 in the EGLN1 gene with COVID-19 severity in Indian population: a novel finding

The present study investigated two single nucleotide polymorphisms (SNPs)—rs479200 and rs516651 in the host EGLN1/PHD2 gene for their association with COVID-19 severity. A retrospective cohort of 158 COVID-19 patients from the Indian population (March 2020 to June 2021) was enrolled. Notably, the frequency of C allele (0.664) was twofold higher than T allele (0.336) in severe COVID-19 patients. Here, we report a novel finding that the C allele of rs479200 in the EGLN1 gene imparts a high risk of severe COVID-19 (odds ratio—6.214 (1.84–20.99) p = 0.003; 9.421 (2.019–43.957) p = 0.004), in additive inheritance model (adjusted and unadjusted, respectively).

Association of the ACTN3 Gene's Single-Nucleotide Variant Rs1815739 (R577X) with Sports Qualification and Competitive Distance in Caucasian Athletes of the Southern Urals.

To study the associations of SNV rs1815739 (C577T or R577X) allelic variants and genotypes of the ACTN3 gene with qualification and competitive distance in Caucasian athletes of the Southern Urals. A total of 126 people of European origin who lived in the Southern Urals region took part in this study. The first group included 76 cyclical sports athletes (speed skating, running disciplines in track-and-field): SD (short distances) subgroup-40 sprinters (mean 22.1 ± 2.4 y.o.); LD (long distances) subgroup-36 stayer athletes (mean 22.6 ± 2.7 y.o.). The control group consisted of 50 healthy nonathletes (mean 21.4 ± 2.7 y.o.). We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. The frequency of the major allele R was significantly higher in the SD subgroup compared to the control subgroup (80% vs. 64%; p-value = 0.04). However, we did not find any significant differences in the frequency of the R allele between the athletes of the SD subgroup and the LD subgroup (80% vs. 59.7%, respectively; p-value > 0.05). The frequency of the X allele was lower in the SD subgroup compared to the LD subgroup (20% vs. 40.3%; p-value = 0.03). The frequency of homozygous genotype RR was higher in the SD subgroup compared to the control group (60.0% vs. 34%; p-value = 0.04). The R allele was associated with competitive distance in the SD group athletes compared to those of the control group (OR = 2.45 (95% CI: 1.02-5.87)). The X allele was associated with competitive distance in the LD subgroup compared to the SD subgroup (OR = 2.7 (95% CI: 1.09-6.68)). Multiplicative and additive inheritance models demonstrated that high athletic performance for sprinters was associated with the homozygous dominant genotype 577RR in cyclical sports athletes of Caucasian origin in the Southern Urals.

Pathogenetic significance of polymorphic variants in the <i>TREM-1</i> gene in the multiple organ failure risk after cardiac surgery

Introduction. Searching of highly specific, sensitive and easy-to-use markers of multiple organ failure (MOF) that will help to the early prognosis of this unfavorable condition, prevent complications and reduce mortality in the early postoperative period is very urgent for the modern medicine.Aim: To study the pathogenetic significance of the TREM-1 gene polymorphism in MOF in patients with coronary artery disease (CAD) in the early postoperative period.Material and methods. 592 CAD patients (564 patients with uncomplicated postoperative period and 28 MOF patients) were selected for the presented study. Genotyping polymorphic variants rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535 and rs2234237 in the TREM-1 gene was carried out by polymerase chain reaction.Results. It was found that the allele T (rs2234246), the allele G (rs1817537) and the allele T (rs3804277) in the TREM-1 gene were associated with an increased MOF risk after elective surgery according to the dominant inheritance model. TREM-1 polymorphic loci rs7768162 and rs4711668 were associated with a decreased MOF risk according to the additive inheritance model. We found no significant associations between polymorphic variants rs2234237, rs6910730, rs9471535, as well as inherited haplotype and MOF risk. Using the MDR analysis, three most significant models of gene-gene interactions of TREM-1 polymorphic loci associated with MOF risk in patients after cardiac surgery were identified.Conclusion. The obtained results demonstrate a significant contribution of polymorphic variants in the TREM-1 gene to the development of MOF in patients undergoing cardiac surgery.

A Pilot Study on the Prevalence of Transcription Factor 7-Like 2 Gene (TCFL2), Rs290487 in Ethnic Groups with Type 2 Diabetes Mellitus in Bayelsa State of Nigeria

The negative impact of type 2 diabetes mellitus (T2DM) on individuals, families, health system and the economic development as a whole, is an important justification for research in this field. The present study is a hospital-based case-control type to ascertain the genetic susceptibility of T2DM among a sample population of various ethnic groups resident in Bayelsa State, Nigeria. Also evaluated was the relationship between transcription factor 7-like 2 (TCFL2) rs12255372 and rs290487 genetic polymorphisms with development of T2DM. Genotyping of TCFL2 rs12255372 and rs290487 were carried out using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Among the indigenous groups, the allelic frequencies determined for the abnormal (CC) and the normal (TT) genotypes were 94.4 and 5.6 (%), respectively; whereas, the values 91.7 and 8.3 (%), in that other, were determined for the non-indigenous groups. A convincing significant difference was found between subjects with T2DMne and their counterpart controls within indigenous people of Bayelsa State with respect to confounders, including age (t=8.046, p<0.00001), BMI (t =2.628, p<0.0190), waist circumference (t=2.800, p=0.0091) and fasting blood sugar (t=3.212, p< 0.0006). This study verified the association of TCFL2 rs290487 with the development of T2DM in indigenous and non-indigenous people in Bayelsa State. The risk conferred by the homozygous CC genotype was higher than that of the heterozygous TC state – a fact indicative of an additive model of inheritance.

Genetic variants of the vitamin D receptor are related to dynapenia in postmenopausal women

BackgroundDynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. AimTo analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women. MethodsWe performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression. ResultsDynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012). ConclusionThis study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women.

TMPRSS2 polymorphism (rs12329760) and the severity of the COVID-19 in Iranian population.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the recent pandemic since early 2020. Due to the wide range of clinical symptoms of this disease, from asymptomatic to severe and critical forms, it seems that genetic differences among patients, along with other factors (such as gender, age, and underlying diseases), can explain part of the variation in disease symptoms. The TMPRSS2 enzyme plays a vital role in the early stages of the interaction of the SARS-CoV-2 with the host cells by facilitating viral entry. There is a polymorphism in the TMPRSS2 gene, called rs12329760(C to T) as a missense variant, which causes the replacement of valine to methionine in the TMPRSS2 protein at position 160. The present study investigated the association between the TMPRSS2 genotype and the severity of the Coronavirus disease 2019 (COVID-19) in Iranian patients. The TMPRSS2 genotype of 251 COVID-19 patients (151 patients with asymptomatic to mild and 100 patients with severe to critical symptoms) was detected on genomic DNA extracted from patients' peripheral blood via the ARMS-PCR method. Our results showed a significant association between the minor T allele and the severity of the COVID-19 (P-value = 0.043) under the dominant and additive inheritance model. In conclusion, the results of this study showed that the T allele of the rs12329760 in the TMPRSS2 gene is a risk allele for severe form of COVID-19 in Iranian patients in contrast to most previous studies on this variant in European ancestry populations which suggested this variant as a protective allele. Our results reiterate to the ethnic-specific risk alleles and hidden unknown complexity behind the host genetic susceptibility. However, further studies are needed to address the complex mechanisms behind the interaction of the TMPRSS2 protein and the SARS-CoV-2 and the role of rs12329760 polymorphism in determining the disease severity.

Дослідження зв'язку фенотипу бронхіальна астма-ожиріння з ER22/23EK і TTH111I поліморфізмами гена глюкокортикоїдного рецептора

(GR) gene with the body mass index (BMI) of patients with bronchial asthma (BA), considering the age of BA onset. Materials and methods. 553 patients with BA and 95 practically healthy persons who previously signed an informed consent to participate in the study were examined. Patients were divided into two clinical groups according to the age of BA onset. Group I included 282 patients with late-onset of asthma (late asthma phenotype), and Group II included 271 patients with early onset (early asthma phenotype). The diagnosis of BA and the severity of the course were established according to the recommendations of GINA-2016 and subsequent versions. Diagnosis of obesity was carried out in accordance with the Order of the Ministry of Health of Ukraine dated August 5, 2009, No. 574, and the European Association for the Study of Obesity (EASO, 2016). The study was approved by the Bioethics Committee of the Medical Institute of Sumy State University. Determination of ER22/23EK (rs 6189/6190) and Tth111I (rs10052957) polymorphisms of the GR gene was performed using the polymerase chain reaction followed by the analysis of restriction fragments. Statistical analysis of the obtained results was carried out using the SPSS-17 program. The results. The analysis of anthropometric parameters showed that among the examined patients with BA, there were 152 (27.5 %) patients with normal body weight (NBW), 206 (37.3 %) were overweight, and 195 (35.2 %) with obesity. Visceral type of obesity was verified among all patients. It was established that among overweight and obese BA patients, there was a higher frequency of GG genotype according to the ER22/23EK polymorphism of the GR gene compared to patients with NBW. Heterozygotes were found 5.6 and 3.5 times more often in patients with normal body weight compared to patients with obesity. Analysis of the ratio of G and A alleles depending on BMI shows a higher frequency of the G allele in obese patients compared to patients with NBW. The distribution of alleles and genotypes according to the Tth111I polymorphism in the examined patients with BA depending on the BMI shows a twice higher frequency of homozygotes for the main C allele in overweight and patients with obesity compared to patients with NBW. Carriers of homozygotes for the minor allele were detected 4.7 times and 2.1 times more often in patients with NBW compared to overweight patients and with obesity. A probable difference in the distribution of alleles and genotypes according to the Tth111I polymorphism of the GR gene was established in patients with early and late BA (p = 0.001). Carriers of homozygotes for the main allele of CC were found more often in patients with early and late BA in the presence of obesity. Conclusions. A higher frequency of the GG genotype according to the ER22/23EK polymorphism of the GR gene and homozygotes according to the main CC allele according to the Tth111I polymorphism of the GR gene in overweight BA patients and with obesity compared to patients with NBW was proven. The protective role of the ER22/23EK polymorphism of the GR gene in relation to the occurrence of obesity in the dominant, superdominant and additive models of inheritance and the Tth111I polymorphism of the GR gene in the superdominant model was established. A higher frequency of carriers of homozygotes for the main C allele in patients with early-onset and late-onset BA in the presence of obesity compared to patients with NBW, a protective role of the Tth111I polymorphism of the GR gene on the risk of developing obesity in patients with late-onset BA in superdominant and recessive models of inheritance was established. Key words: bronchial asthma, obesity, onset, course, ER22/23EK, and Tth111I polymorphisms of the glucocorticoid receptor gene.

GLN27GLU POLYMORPHISM IN THE Β2-ADRENORECEPTOR GENE IN PATIENTS WITH ASTHMA WITH REGARD TO THE AGE OF ONSET

Aim: The study aimed to assess the frequency of the Gln27Glu polymorphic variant in the β2-AR gene among patients with early and late-onset asthma and assess asthma risks depending on the disease phenotype. Materials and Methods: Our study included a total of 553 asthma patients who consented to participate in the study. Asthma was diagnosed according to the 2016 GINA recommendations and its later versions. The study was approved by the Bioethics Committee of the Medical Institute of Sumy State University. The analysis for determining genetic polymorphism (designated as rs1042714) was conducted through the use of polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of obtained results was performed using SPSS–17 program. Results: It was found that there is a significant difference in the distribution of alleles and genotypes in people with early-onset asthma compared to those with late-onset asthma; the statistical analysis showed a χ2 value of 41.75 and p-value of 0.001 for early-onset asthma, and a χ2 value of 44.24 and p-value of 0.001 for late-onset asthma. We did not observe a significant increase in the early-onset asthma risk with an account of different inheritance models connected to the studied polymorphism. Research that took into account the risk of late-onset asthma discovered statistically significant results regarding the dominant (p = 0.001), super-dominant (p = 0.001), and additive (p = 0.001) models of inheritance. Conclusions: Based on the data collected, it was found that individuals carrying the minor allele (both homozygotes and heterozygotes) were at a greater risk of developing asthma later in life. However, no such correlation was observed in patients with early-onset asthma.

Association of Polymorphism rs12778366 of the SIRT1 Gene with the Risk of Age-Related Macular Degeneration

The C allele in the additive inheritance model and the TC heterozygous genotype in the codominant and recessive models serve as the genetic factor predisposing to this disease (p&lt;0,001, OR: 2,121, 95% of CI: 1.435-3.133; p&lt;0.001, OR: 2.499, 95% of CI: 1.595-3.915; p&lt;0.001, OR: 2.507, 95% of CI: 1.612-3.900). In addition, the C allele was more common in women with AMD and in AMD patients over 65 years of age, which may be associated with a higher risk of AMD

Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease

BackgroundIschemic coronary heart disease (IHD) is the leading cause of death worldwide. Genetic variation is presumed to be a major factor underlying sex differences for IHD events, including mortality. The purpose of this study was to identify sex-specific candidate genes associated with all-cause mortality among people diagnosed with coronary artery disease (CAD). MethodsWe performed a sex-stratified, exploratory genome-wide association (GWAS) screen using existing data from CAD-diagnosed males (n = 510) and females (n = 174) who reported European ancestry from the Duke Catheterization Genetics biorepository. Extant genotype data for 785,945 autosomal SNPs generated with the Human Omni1-Quad BeadChip (Illumina, CA, USA) were analyzed using an additive inheritance model. We estimated instantaneous risk of all-cause mortality by genotype groups across the 11-year follow-up using Cox multivariate regression, covarying for age and genomic ancestry. ResultsThe top GWAS hits associated with all-cause mortality among people with CAD included 8 SNPs among males and 15 among females (p = 1 × 10−6 or 10−7), adjusted for covariates. Cross-sex comparisons revealed distinct candidate genes. Biologically relevant candidates included rs9932462 (EMP2/TEKT5) and rs2835913 (KCNJ6) among males and rs7217169 (RAP1GAP2), rs8021816 (PRKD1), rs8133010 (PDE9A), and rs12145981 (LPGAT1) among females. ConclusionsWe report 20 sex-specific candidate genes having suggestive association with all-cause mortality among CAD-diagnosed subjects. Findings demonstrate proof of principle for identifying sex-associated genetic factors that may help explain differential mortality risk in people with CAD. Replication and meta-analyses in larger studies with more diverse samples will strengthen future work in this area.

Association of Sirtuin 1 Gene Polymorphisms with the Risk of Coronary Heart Disease in Chinese Han Patients with Type 2 Diabetes Mellitus.

Aims To explore the associations between polymorphisms in SIRT1 and coronary heart disease (CHD) risk in Chinese Han patients with type 2 diabetes (T2D). Methods This case-controlled study enrolled 492 patients with T2D: 297 with CHD and 195 without CHD. Five SIRT1 haplotype-tagging single-nucleotide polymorphisms (rs3818291, rs12242965, rs3818292, rs4746720, and rs16924934) were selected from Chinese Han data in the GRCh37.p13 phase 3 database and genotyped by polymerase chain reaction-restriction fraction length polymorphism or sequencing. Results The rs16924934 G allele was associated with a higher risk of CHD than the A allele (odds ratio (OR) = 1.429; 95% confidence interval (CI) = 1.003–2.037; P = 0.048). Using an additive inheritance model, the rs3818291 G/A genotype was associated with a higher CHD risk than the G/G genotype (OR′ = 1.683; 95%CI = 1.033–2.743; P′ = 0.037 after adjustment for CHD risk factors). Smokers carrying G/A or A/A rs3818291 genotypes had a 3-fold higher CHD risk than those carrying GG (adjusted OR′ = 3.035; P′ = 0.011) and a 2.6-fold higher CHD risk than nonsmokers carrying GG (adjusted OR′ = 2.604; P′ = 0.033). Conclusions Genetic polymorphisms of SIRT1 are associated with the risk of CHD in a Chinese Han population with T2D.

Analysis of the redistribution of rs4977574-polymorphic variants of the ANRIL gen in patients with acute coronary syndrome of different sex

Annotation. The aim of the study was to analyze the distribution of rs4977574-polymorphic variants of the ANRIL gene in patients with acute coronary syndrome of different sex. The venous blood of 234 patients with acute coronary syndrome (ACS) and 195 people without cardiac pathology was used for the study. DNA was isolated from whole venous blood using the GeneJET Whole Blood Genomic DNA Purification Mini Kit (ThermoFisher Scientific, USA). rs4977574 ANRIL gene polymorphism was studied by real-time PCR reaction in the presence of TaqMan assay C_31720978_30. Statistical analysis of the study was performed using the SPSS program (version 17.0). A difference was found when comparing the frequencies of genotypes at the polymorphic site rs4977574 of the ANRIL gene in their distribution (p=0,035). According to the results of logistic regression, it was detected that in the recessive (p=0,015) and additive (p=0,012) inheritance models, carriers of the G/G genotype are approximately 2 times more likely to develop ACS than carriers of the A-allele. The reliability of the results was maintained after adjustments for gender, age, B&lt;I, smoking habits, diabetes and stress (p=0,049 for the recessive model; p=0,037 for the additive model). Thus, individuals with the rs4977574 G/G genotype polymorphism of the ANRIL long non-coding RNA gene have a 2 times higher risk of developing ACS than dominant allele carriers. Further research will focus on the association of ANRIL polymorphism with the risk of ACS depending on other risk factors.

Common variants in AGR1 genes contributed to the risk and traits of cirrhotic cardiomyopathy in the Han Chinese population.

Aim: This study aimed to determine the association between polymorphisms of the ARG1 gene and the risk and traits of cirrhotic cardiomyopathy (CCM). Methods: A total of 468 CCM and 1012 cirrhosis patients were enrolled, and 12 single-nucleotide polymorphisms (SNPs) in the ARG1 gene were genotyped. Differences in genotype, allele and haplotype frequencies of the SNPs between the CCM and cirrhosis groups were analyzed by chi-square test. Correlations of the genotypes of SNPs and representative traits of liver and heart function were performed using linear regression analysis. Results: SNPs rs2781666 and rs2781667 were associated with the risk of CCM in both dominant and additive inheritance models. The GG genotype frequency of rs2781666 and CC genotype frequency of rs2781667 were lower in the CCM group than in the cirrhosis group. The G-C haplotype frequency of the block consisting of rs2781666 and rs2781667 was higher and the T-T haplotype frequency was lower in CCM patients than in cirrhosis patients. SNP rs2781666 was associated with the alanine transaminase level, and rs2781667 was associated with the ARG1 level and left atrial diameter. Conclusion: SNPs rs2781666 and rs2781667 in the ARG1 gene were associated with susceptibility to and traits of CCM in the Han Chinese population.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (K121Q rs1044498) polymorphism is associated with diabetic nephropathy but not obesity among type-2 diabetes mellitus Egyptian patients

IntroductionGenetics contribute to the development of type-2 diabetes mellitus (T2DM), its complications, and phenotypes such as diabetic nephropathy (DN) and obesity. Although the likely associations among the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, DN and obesity have been massively investigated, the results are still controversial. This study aimed to assess whether ENPP1 K121Q (A/C rs1044498) variant is associated with DN and obesity in T2DM Egyptian patients. We genotyped this variant in a total of 183 T2DM Egyptian patients who were classified into cases (91 participants with moderately increased albuminuria or severely increased albuminuria ≥ 30 mg/g) and controls (92 patients with normoalbuminuria <30 mg/g) using TaqMan technology.ResultsPatients, with the C (minor/risk) allele, had significantly higher moderately increased albuminuria/severely increased albuminuria levels (P < 0.001) and albumin-to-creatinine ratio (P = 0.001) than those with the wild A allele. AC and CC genotypes of ENPP1 K121Q (A/C, rs1044498) variant and its C-allele frequencies are significantly higher in cases than controls (P = 0.043 and 0.013), respectively, and in patients with estimated glomerular-filtration rate (eGFR) less than 60 than those with eGFR more than 60 (P = 0.014 and 0.004), respectively. AC and CC genotypes are associated with cases with a significant odds ratio in both dominant [odds ratio (OR): 2.003, 95% confidence interval (CI): 1.106–3.628, P = 0.022) and additive (OR: 1.865, 95% CI: 1.134–3.070, P = 0.014) models of inheritance and in patients with eGFR less than 60 in the dominant model of inheritance (OR: 2.398, 95% CI: 1.258–4.571, P = 0.008), but showed no association with obesity (P > 0.05).ConclusionENPP1 K121Q (A/C, rs1044498) variant is associated with DN but not obesity among Egyptian T2DM patients.

ANALYSIS OF THE ASSOCIATION OF RS4977574-POLYMORPHIC VARIANTS OF THE ANRIL GENE WITH THE DEVELOPMENT OF ACUTE CORONARY SYNDROME IN INDIVIDUALS WITH DIFFERENT BODY MASS INDEX IN THE UKRAINIAN POPULATION

The objective was to analyze the association of rs4977574-polymorphic variants of the ANRIL gene with the development of acute coronary syndrome in individuals with different body mass index. Materials and methods. The venous blood of 429 people (234 patients with acute coronary syndrome and 195 people in the control group) was used for the study. Genotyping of patients by rs4977574-polymorphic variants of the ANRIL gene was performed by real-time polymerase chain reaction (Real-time PCR) in the presence of TaqMan assay C_31720978_30. Statistical analysis of the results of the study was performed using SPSS software (version 17.0). Results. The distribution of genotypes according to SNP rs4977574 of the ANRIL gene in the group of patients with ACS and the control group among individuals with BMI &lt; 25 kg/m2 does not differ. Among patients with BMI 25 kg/m2 the genotype distribution of the rs4977574-polymorphic variant of the ANRIL gene was statistically significant (р = 0.035). In the group of patients with BMI &gt; 25 kg/m2 according to recessive (Pobserv = 0.014; ORobserv = 1.876, 95 % СІ = 1.137–3.095) and additive (Рobserv = 0.014; ORobserv = 2.118, 95% СІ = 1.166–3.849) models of inheritance before making adjustment, people with G/G genotype had a double risk of acquiring ACS than carriers of the dominant allele. After the adjustment, corresponding models of inheritance had the same risk rate – for recessive model (Рadjust = 0.013; ORadjust = 1.951, 95% СІ = 1.149–3.313) and additive model (Рadjust = 0.026; ORadjust = 2.039, 95 % СІ = 1.087–3.826). Conclusions. Individuals with BMI &gt; 25 kg/m2, which were carriers of G/G genotype had a 2 times higher risk to acquire ACS than the individuals with the dominant allele. Prospects for further research. Further research will be aimed at studying the impact of ANRIL polymorphism upon the risk of ACS development depending on other risk factors.