Allelic Association Research Articles

APOEε4, in-hospital delirium and long-term cognitive impairment: A longitudinal memory clinic study

IntroductionDelirium is common among hospitalized elderly. Previous short-term studies reported inconsistent associations between APOEε4 allele, in-hospital delirium, and post-delirium cognitive impairment. We examined the association of APOEε4 allele with in-hospital delirium and long-term cognitive outcomes following delirium. MethodsThe electronic medical records were linked to the Korean National Health Insurance Service database of all citizens from January 2002 to July 2019. The study population consisted of 1057 memory clinic visitors with APOE genotype, longitudinal neuropsychological tests, and hospitalization records. Incident in-hospital delirium was defined as the initiation of antipsychotics during hospitalization after excluding prevalent users. Incidence analysis was conducted using Cox proportional hazards models, while longitudinal outcomes were analyzed using multivariable mixed models with an interrupted time series design. ResultsAt baseline, APOEε4 carriers (N = 298, 28.2%) performed poorly on cognitive tests compared to non-carriers (CDR-SB mean±SD: 3.3 ± 3.5 vs 2.8 ± 2.9, P = 0.016; MMSE 22.3 ± 5.8 vs 23.2 ± 5.2, P = 0.029). The carriers developed more in-hospital delirium than noncarriers after covariate adjustments (HR 1.96, 95%CI 1.30–2.96, P = 0.002). The APOEε4 allele also had a more detrimental impact on four out of the five cognitive and functional measurements after the delirium (beta estimates of post-delirium change by APOEε4 for CDR-SB = 3.20, P < 0.001; CDR = 0.60, P < 0.001; KIADL = 0.99, P < 0.001; SIADL = 14.07, P < 0.001). These findings remained robust even after adjusting for covariates. ConclusionsAPOEε4 carriers demonstrated robust associations with in-hospital delirium and exhibited more post-delirium cognitive and functional impairment compared to non-carriers. Individuals with APOEε4 allele may need more attention to prevent in-hospital delirium and post-delirium cognitive and functional deterioration.

Rare peptide anchors of HLA class I alleles contribute to the COVID-19 disease severity and T cell memory

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Associations Between Osteopontin Variants and Systemic Lupus Erythematosus: A Meta-Analysis.

Objective: Osteopontin (OPN) increases T cell proliferation, interferon production, and CD40 ligand expression, which leads to B cell proliferation and antibody production. This study aimed to determine whether OPN variants are associated with susceptibility to systemic lupus erythematosus [SLE]. Methods: We searched the Medline, Embase, and KoreaMed databases for available articles. We performed a meta-analysis on the association of OPN 707 T/C (rs1126616) at exon 6, 1083 G/A (rs112772) at the 3'-untranslated region (3'-UTR), 1239 C/A (rs9138) at 3'-UTR, and 9250 T/C (rs11229919) variants in exon 7 with susceptibility to SLE. Results: Ten studies from 9 articles with 2175 SLE patients and 3233 controls were included. The meta-analysis showed a significant association between SLE and the 707 T allele of the OPN 707 T/C variant (odds ratio [OR] = 1.522, 95% confidence interval [CI] = 1.101-2.105, p = 0.044). Stratification by ethnicity indicated an association between the OPN 707 T/C variant and SLE in European and Arab populations. A meta-analysis revealed a significant association between the OPN 9250 C allele and SLE in the Asian and Arab populations. A significant association was also identified between the +1239 C allele of the OPN 1239 C/A variant and SLE (OR = 1.192, 95% CI = 1.008-1.410, p = 0.040). The meta-analysis indicated no allelic association between SLE and OPN 1083 G/A and OPN 1239 C/A variants. Conclusions: The OPN 707 T/C variant is associated with SLE susceptibility in European and Arab populations and the OPN 9250 T/C variant is associated with SLE susceptibility in Asian and Arab populations. In addition, associations were found between the OPN 1239 C/A variant and SLE.

Sex-based differences in metabolic protection by the ANP genetic variant rs5068 in the general population.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are produced in the heart and secreted into the circulation. As hormones, both peptides activate the guanylyl cyclase receptor A (GC-A), playing a role in blood pressure (BP) regulation. A significant role for ANP and BNP includes favorable actions in metabolic homeostasis. Sex-based high prevalence of risk factors for cardiovascular disease in males compared with females is well established, but sex-based differences on cardiometabolic protection have not been investigated in relation to ANP (NPPA) and BNP (NPPB) gene variants. We included 1,146 subjects in the general population from Olmsted County, Minnesota. Subjects were genotyped for the ANP gene variant rs5068 and BNP gene variant rs198389. Cardiometabolic parameters and medical records were reviewed. In the presence of the minor allele of rs5068, diastolic BP, creatinine, body mass index (BMI), waist measurement, insulin, and prevalence of obesity and metabolic syndrome were lower, whereas HDL was higher in males with only trends observed in females. We observed no associations of the minor allele with echocardiographic parameters in either males or females. Regarding rs198389 genotype, the minor allele was not associated with any BP, metabolic, renal, or echocardiographic parameters in either sex. In the general community, the minor allele of the ANP gene variant rs5068 is associated with a favorable metabolic phenotype in males. No associations were observed with the BNP gene variant rs198389. These studies support a protective role of the ANP pathway on metabolic function and underscore the importance of sex in relationship to natriuretic peptide responses.NEW & NOTEWORTHY Males are characterized by lower ANP and BNP with greater prevalence of cardiometabolic disease. The ANP genetic variant rs5068 was associated with less metabolic dysfunction in males, whereas no metabolic profile was related to the BNP genetic variant rs198389 in the general population. ANP may play a more biological role in metabolic homeostasis compared with BNP in the general population with greater physiological metabolic actions in males compared with females.

DNA repair genes, air pollution, and breast cancer risk

PurposeWe investigated if selected polymorphisms in DNA repair genes modify the association between air pollution and breast cancer (BCa) risk. MethodsWe included 150,929 postmenopausal women (5969 with BCa) from UK Biobank, a population-based prospective cohort. Information on BCa risk factors was collected at baseline. Cox proportional hazards regression was used to examine interactions of exposure for which we previously found associations with BCa in this cohort (2007 PM10 and cumulative average PM10) with 15 SNPs, adjusting for BCa risk factors. The associations between PM10 and BCa risk were stratified by genotype level. ResultsThe positive associations of 2007 PM10 and cumulative average PM10 with BCa risk were stronger in women with one or two copies of XRCC2 rs3218536C allele versus none (2007 PM10 Hazard Ratio (HR) per 1 µg/m3 = 1.04, 95% Confidence Interval (CI) 1.02–1.07, HR = 1.01, 95% CI 1.00–1.02, respectively, versus HR = 0.94, 95% CI 0.83–1.06, p-interaction = 0.02; cumulative average PM10 HR per 1 µg/m3 = 1.11, 95% CI 1.07–1.15, HR = 1.07, 95% CI 1.05–1.08 versus HR = 0.92, 95% CI 0.78–1.09, p-interaction = 0.05). The association of cumulative average PM10 with BCa was stronger in women with two copies of XRCC1 rs25489 T allele versus one or none (HR = 3.04, 95% CI 1.54–5.96 vs. HR = 1.06, 95% CI 1.02–1.11 and HR = 1.07, 95% CI 1.06–1.09; p-interaction = 0.06). ConclusionsOur results suggest stronger associations of 2007 PM10 and cumulative average PM10 with postmenopausal BCa risk in carriers of XRCC2 rs3218536C allele and stronger associations of cumulative average PM10 in those with two copies of XRCC1 rs25489 T allele.

Association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women in India

BackgroundHuman leukocyte antigen (HLA) restriction plays an important role in the susceptibility to alloimmunization against red blood cell (RBC) antigens. The prevalence of anti-D alloimmunization in RhD negative pregnancy is still quite high in our population. Thus, we planned this study to determine the association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women. Material and methodsRBC antibody screen (ABS) was performed for RhD negative pregnant women attending the antenatal clinic our institute. Those with a negative result were included in the ‘non-alloimmunized’ (NAL) group (‘Control’ group), while those with anti-D alloantibody on performing antibody identification were included in the alloimmunized (AL) group of the study (n = 50 each). ABS and identification were done using column agglutination technique. The HLA-DRB1 typing was done by Luminex based reverse sequence specific oligonucleotide probing (SSOP) using commercial kits. The HLA-DRB1 allele frequency was compared in both the groups. ResultsThere was a significant difference between the two groups in terms of gravida (p < 0.001) and history of anti-D immunoprophylaxis (p < 0.001). The frequency of HLA-DRB1*03 and HLA-DRB1*04 alleles was significantly higher in the AL group than the NAL group: 40 % versus 18 % [Odds Ratio (OR): 3.04, 95 % CI: 1.21–7.6; p = 0.015] for HLA-DRB1*03 alleles and 18 % versus 4 % (OR: 5.27, 95 % CI: 1.08–25.78, p = 0.025) for HLA-DRB1*04 alleles. ConclusionThe frequency of HLADRB1*03 and HLADRB1*04 alleles was significantly higher in RhD negative pregnant women alloimmunized with anti-D alloantibody.

Analysis of Cdx2 VDR gene polymorphism rs11568820 in association with multiple sclerosis in Slovaks

ABSTRACT Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of the vitamin D receptor (VDR) that binds the vitamin D responsive elements of target genes including HLA-DRB1*15. The aim of the present study in Slovaks was to analyse the association of Cdx-2 variants with the risk of MS and disability progression, and to assess the DRB1*15:01 allele as a possible confounding factor. In total, 493 MS patients and 417 healthy controls were involved in this study. The genotyping of Cdx-2 was performed using restriction analysis; DRB1*15:01 positivity was determined by a high-resolution melting analysis of its surrogate marker rs3135388 (G/A). Our results did not prove any allelic association between Cdx-2 and a risk of MS (minor allele A − 0.181 in patients vs. 0.161 in controls, OR = 1.15, .95 CI = 0.90–1.47, p = 0.289). The logistic regression analysis, adjusted for sex and age, showed no differences in Cdx-2 genotype counts when using an additive, dominant or recessive genetic model (p = 0.351, 0.150, 0.240 respectively). The Cdx-2 variants were also not associated with disease disability progression, evaluated using the Multiple Sclerosis Severity Score. The HLA-DRB1*15:01 allele was found to strongly increase the risk of MS in our study (0.300 in patients vs. 0.101 in controls, OR = 3.83, .95 CI = 2.94–4.99, p = 1.016 × 10−26, dominant genetic model OR = 4.62, .95 CI = 3.40–6.26, p = 9.1 × 10−23). In summary, we found the Cdx-2 as a single genetic marker not to be associated with MS development or progression in Slovaks, independently of HLA-DRB1*15:01 status.

Race-specific association of an IRGM risk allele with cytokine expression in human subjects

Immunity-related GTPase family M (IRGM), located on human chromosome 5q33.1, encodes a protein that promotes autophagy and suppresses the innate immune response. The minor allele of rs13361189 (−4299T>C), a single nucleotide polymorphism in the IRGM promoter, has been associated with several diseases, including Crohn’s disease and tuberculosis. Although patterns of linkage disequilibrium and minor allele frequency for this polymorphism differ dramatically between subjects of European and African descent, studies of rs13361189 have predominantly been conducted in Europeans and the mechanism of association is poorly understood. We recruited a cohort of 68 individuals (30 White, 34 African American, 4 other race) with varying rs13361189 genotypes and assessed a panel of immune response measures including whole blood cytokine induction following ex vivo stimulation with Toll-like Receptor ligands. Minor allele carriers were found to have increased serum immunoglobulin M, C-reactive protein, and circulating CD8+ T cells. No differences in whole blood cytokines were observed between minor allele carriers and non-carriers in the overall study population; however, minor allele status was associated with increased induction of a subset of cytokines among African American subjects, and decreased induction among White subjects. These findings underline the importance of broad racial inclusion in genetic studies of immunity.

Dried blood spot-based host genome analysis technique targeting pathological associations with hepatitisB: Development and clinical application in the Cambodian population.

Reports of patients with hepatitisB have highlighted associations between polymorphisms in the human leukocyte antigen (HLA)-DPB1, CXCL13, and CXCR5 genes and disease pathology. Owing to its potential to contribute to the development of new diagnostic and therapeutic methods, we aimed to establish a reliable host genome analysis technique that can be used in countries with inadequate infrastructure. We compared multiple commercially available kits for dried blood spot (DBS)-based sample collection to develop a basic DBS-based host genome analysis technique. We then collected blood samples from Cambodian patients with hepatitis B and performed single-nucleotide polymorphism genotyping and HLA allele typing by the DBS system. We were able to perform single-nucleotide polymorphism genotyping and HLA allele typing with host DNA samples obtained using a combination of a HemaSpot™ filter paper-based device and a SMITEST® EX-R&D DNA extraction kit. The accuracy of genotyping using samples obtained by this method was not inferior to one using samples obtained by venipuncture. In the Cambodian population, significant associations of HLA-DPB1*04:01 with protection against chronic hepatitisB virus (HBV) infection, and HLA-DPB1*05:01 and HLA-DPB1*13:01 with susceptibility to chronic HBV infection were identified. Based on the DBS system, we clarified the associations of HLA-DPB1 alleles with chronic HBV infection in the Cambodian population for the first time. Because the DBS is a low-cost, durable, transportable, and easy-to-handle modality, genetic analysis based on the DBS system is a feasible strategy for obtaining a deeper understanding of HBV epidemiology, especially in middle- or low-income countries.

Interleukin 10 (IL-10) gene variants and haplotypes in Tunisian women with polycystic ovary syndrome (PCOS): a case-control study.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women in their child-bearing age, and is associated with insulin resistance and type 2 diabetes. The etiology of PCOS involves multiple factors including genetic, metabolic and immunological factors. Interleukin - 10 (IL-10), as an anti-inflammatory cytokine, plays a critical role in this regard. We investigated the potential role of IL-10 gene variants in the development of PCOS in Tunisian population. 115 cases and 120 controls were recruited in the current case control study. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping for IL-10, rs1800896, rs1800871 and rs1800872 variants, was performed by real time PCR. The results obtained showed that the minor allele frequency of rs1800896, rs1800871and rs1800872 were comparable between PCOS cases and control subjects (P = 0.30, P = 0.71, and P = 0.57 respectively). The distribution analysis revealed an unsignificant association of the three tested variants, in all genetic models. Haplotype analysis identified one haplotype CCA with a protective role in PCOS development (P = 0.05; OR (95% CI) = 0.56 (0.32 - 0.99)). This association did not persist after adjustment for multiples covariates (Pc = 0.154). Our study is the first to show how ethnicity influences the association of IL-10 gene variants with PCOS susceptibility. No allelic nor genetic association were observed between the tested variants and PCOS in Tunisian women, however, a particular IL-10 haplotype with a protective effect for PCOS was identified.

Associations of classical HLA alleles with depression and anxiety.

Immune dysregulation has been widely observed in patients with psychiatric disorders. This study aims to examine the association between HLA alleles and depression and anxiety. Using data from the UK Biobank, we performed regression analyses to assess the association of 359 HLA alleles with depression and anxiety, as determined by Patient Health Questionnaire (PHQ) score (n = 120,033), self-reported depression (n = 121,685), general anxiety disorder (GAD-7) score (n = 120,590), and self-reported anxiety (n = 108,310). Subsequently, we conducted gene environmental interaction study (GEIS) to evaluate the potential effects of interactions between HLA alleles and environmental factors on the risk of depression and anxiety. Sex stratification was implemented in all analysis. Our study identified two significant HLA alleles associated with self-reported depression, including HLA-C*07:01 (β = -0.015, p = 5.54 × 10-5 ) and HLA-B*08:01 (β = -0.015, p = 7.78 × 10-5 ). Additionally, we identified four significant HLA alleles associated with anxiety score, such as HLA-DRB1*07:01 (β = 0.084, p = 9.28 × 10-5 ) and HLA-B*57:01 (β = 0.139, p = 1.22 × 10-4 ). GEIS revealed that certain HLA alleles interacted with environmental factors to influence mental health outcomes. For instance, HLA-A*02:07 × cigarette smoking was associated with depression score (β = 0.976, p = 1.88 × 10-6 ). Moreover, sex stratification analysis revealed significant sex-based differences in the interaction effects of certain HLA alleles with environmental factors. Our findings indicate the considerable impact of HLA alleles on the risks of depression and anxiety, providing valuable insights into the functional relevance of immune dysfunction in these conditions.

NEFA Dynamics in Adults With Severe Obesity and Insulin Resistance: No Coupling to the rs9939609 FTO Risk Allele.

The FTO gene is highly expressed in adipose tissues; however, whether nonesterified fatty acids (NEFA) dynamics are impacted by FTO has not been rigorously tested for in a uniformly obese study population comprising both sexes. To test for associations of the rs9939609 FTO risk allele with NEFA suppression. We investigated 97 subjects with severe obesity but without diabetes, having genotype TT (n = 32), AT (n = 31), or AA (n = 34) in a cross-sectional observation study. NEFA suppression was assessed from a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer as well as from the response to a standardized meal. Insulin sensitivity was assessed by hepatic and total insulin sensitivity measurements in the clamp and by the Matsuda index during the meal. Variables of possible importance for NEFA dynamics were primarily assessed by linear regression. No genotype associations with fasting or suppressed NEFA were found, whether in the clamp or meal situation (P > .7 for all comparisons). Independent of genotype, higher fasting concentrations of NEFA and larger NEFA suppression were found in female compared with male subjects. Fasting NEFA or degree of suppression were not associated with total fat mass or body mass index. The respiratory quotient was negatively associated with NEFA suppression. In a gender-mixed adult population of obese individuals, an FTO obesity-risk allele did not affect fasting NEFA nor suppression thereof. These negative results on NEFA dynamics appear strengthened by the documentation of gender influence and associations with parameters reflective of insulin resistance.

Fifty years after the discovery of the association of HLA B27 with ankylosing spondylitis

The human lymphocyte antigen B27 (HLA B27) is a member of the HLA class I family of genes in the major histocompatibility complex whose name goes back to its discovery...

Somatic cell structural variant mutagenesis and neurologic disease

Detection of organismal mosaic states for variant alleles faces technical and analytical challenges, as does the association of such variant alleles with susceptibility to neurologic disease. In this issue of Cell Genomics, Maury etal.1 reanalyze genotyping arrays of a schizophrenia cohort providing evidence for the contribution of somatic structural variant mutagenesis and rare variant alleles.

Large-scale identification of undiagnosed hepatic steatosis using natural language processing

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity in people with and without diabetes, but it is underdiagnosed, posing challenges for research and clinical management. Here, we determine if natural language processing (NLP) of data in the electronic health record (EHR) could identify undiagnosed patients with hepatic steatosis based on pathology and radiology reports. A rule-based NLP algorithm was built using a Linguamatics literature text mining tool to search 2.15 million pathology report and 2.7 million imaging reports in the Penn Medicine EHR from November 2014, through December 2020, for evidence of hepatic steatosis. For quality control, two independent physicians manually reviewed randomly chosen biopsy and imaging reports (n=353, PPV 99.7%). After exclusion of individuals with other causes of hepatic steatosis, 3007 patients with biopsy-proven NAFLD and 42,083 patients with imaging-proven NAFLD were identified. Interestingly, elevated ALT was not a sensitive predictor of the presence of steatosis, and only half of the biopsied patients with steatosis ever received an ICD diagnosis code for the presence of NAFLD/NASH. There was a robust association for PNPLA3 and TM6SF2 risk alleles and steatosis identified by NLP. We identified 234 disorders that were significantly over- or underrepresented in all subjects with steatosis and identified changes in serum markers (e.g., GGT) associated with presence of steatosis. This study demonstrates clear feasibility of NLP-based approaches to identify patients whose steatosis was indicated in imaging and pathology reports within a large healthcare system and uncovers undercoding of NAFLD in the general population. Identification of patients at risk could link them to improved care and outcomes. The study was funded by US and German funding sources that did provide financial support only and had no influence or control over the research process.

Effects of the Trp64Arg Polymorphism in the ADRB3 Gene on Body Composition, Cardiorespiratory Fitness, and Physical Activity in Healthy Adults.

The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, overweight individuals, and obese and diabetic patients, but it has not been studied in young and healthy adults so far. In the present study, we examined the association of ADRB3 rs4994 polymorphism with body composition, somatotype, cardiorespiratory fitness and physical activity in young, healthy adults (N = 304). All subjects had anthropometric measurements, and somatotypes were assessed using the Heath-Carter method. In addition, cardiorespiratory fitness and physical activity levels were assessed. Genotyping for the ADRB3 gene was performed using a PCR-RFLP method. In the male group, body components were associated with the Trp64Trp genotype (waist circumference (p = 0.035), hip circumference (p = 0.029), BF (%) (p = 0.008), and BF (kg) (p = 0.010), BMI (p = 0.005), WHtR (p = 0.021), and BAI (p = 0.006)). In addition, we observed that the Trp64Trp genotype was associated with somatotype components (p = 0.013). In contrast, the Arg allele was associated with the ectomorphic components (0.006). We also observed a positive impact of the Trp64Trp genotype with maximal oxygen uptake (p= 0.023) and oxygen pulse (p = 0.024). We observed a negative relationship of the Trp64Trp genotype in the female group with reported moderate-intensity exercise (p = 0.036). In conclusion, we found an association of the Trp64 allele with anthropometric traits, somatotype and parameters describing physical performance in the male group. In the female subpopulation, we only found an effect of the polymorphism Trp64Arg on the level of physical activity for moderate-intensity exercise.

Single Nucleotide Polymorphisms Associated with Rheumatoid Arthritis in Saudi Patients.

This study included 105 patients with RA and an equal number of age- and sex-matched controls. The patients with RA attended outpatient clinics at King Khalid University Hospital in Riyadh, Saudi Arabia. Blood samples were collected, and DNA was extracted using Qiagen kits. Primers were designed for the 33 selected SNPs using the MassEXTEND primers program, and samples were genotyped on the Sequenom MassARRAY iPLEX platform. The allele frequencies and genotypes were determined for each SNP, and the results obtained for the patients were compared to those for the controls. The allele and genotype frequencies of six SNPs were significantly associated with RA: rs1188934, rs10919563, rs3087243, rs1980422, rs10499194, and rs629326. The minor alleles of rs1188934, rs10919563, rs10499194, and rs629326 were protective, with odds ratios of 0.542, 0.597, 0.589, and 0.625, and p-values of 0.002, 0.023, 0.013 and 0.036, respectively. In addition, the heterozygote frequencies of two SNPs (rs6859219 and rs11586238) were significantly higher in the controls than in the patients. There is considerable heterogeneity in the genetics of RA in different populations, and the SNPs that are associated with RA in some populations are not in others. We studied 33 SNPs and only eight were associated with RA. The remaining SNPs showed no allelic or genotypic associations with RA.

HLA-G Alleles Impact the Perinatal Father-Child HPV Transmission.

The host factors that influence father-to-child human papillomavirus (HPV) transmission remain unknown. This study evaluated whether human leukocyte antigen (HLA)-G alleles are important in father-to-child HPV transmission during the perinatal period. Altogether, 134 father-newborn pairs from the Finnish Family HPV Study were included. Oral, semen and urethral samples from the fathers were collected before the delivery, and oral samples were collected from their offspring at delivery and postpartum on day 3 and during 1-, 2- and 6-month follow-up visits. HLA-G alleles were tested by direct sequencing. Unconditional logistic regression was used to determine the association of the father-child HLA-G allele and genotype concordance with the father-child HPV prevalence and concordance at birth and during follow-up. HLA-G allele G*01:01:03 concordance was associated with the father's urethral and child's oral high-risk (HR)-HPV concordance at birth (OR 17.00, 95% CI: 1.24-232.22). HLA-G allele G*01:04:01 concordance increased the father's oral and child's postpartum oral any- and HR-HPV concordance with an OR value of 7.50 (95% CI: 1.47-38.16) and OR value of 7.78 (95% CI: 1.38-43.85), respectively. There was no association between different HLA-G genotypes and HPV concordance among the father-child pairs at birth or postpartum. To conclude, the HLA-G allele concordance appears to impact the HPV transmission between the father and his offspring.

Analysis of Molecular Genetic Markers of Osteoporosis in Residents of the Russian Federation

Relevance. Osteoporosis is a multifactorial disease with a high level of disability, which is a serious health problem worldwide. High prevalence and disability rates are associated not only with the peculiarities of the course of this pathology, but also with the untimely diagnosis and initiation of therapy. Therefore, it is extremely relevant to search for specific and accessible markers of osteoporosis, such as molecular genetic markers or single-nucleotide polymorphisms, analysis of which will help identify risk factors for disease development before clinical symptoms manifest during patient examinations.Aims. This study is aimed at finding risk factors for the development of HCG in patients with gastritis and the relationship of polymorphisms of various genes with the development of this pathology.Materials and methods. A search was made for the association with osteoporosis of singlenucleotide polymorphisms of the genes: COL1A1, CYP2R1, ESR1, LCT, LRP5, VDR in residents of the Russian Federation (n = 669). Polymorphic markers of candidate genes were selected for research based on the presence of associations with osteoporosis according to previously conducted studies published in the RSCI, PubMed, Web of Science, MEDLINE, Scopus databases, as well as on the results of monitoring polymorphisms included in the panels of genetic predisposition to osteoporosis of companies engaged in genetic testing in the Russian Federation. Two groups were formed for the study: the main (case) – 234 patients with an established diagnosis of Osteoporosis, the control – 435 patients selected using a random number generator from conditionally healthy individuals from the Basis Genomic Group database (Basis Genomics LLC). The groups were comparable in age and gender (p &gt; 0.05).Statistical analysis was carried out using the StatTech v. 3.1.6. program (developed by Stattech LLC, Russia). The nature of the distribution of quantitative data was checked by the Shapiro-Wilk, Kolmogorov-Smirnov criteria, the statistical significance of differences in 2 independent groups was assessed using the Mann-Whitney U-test. The ꭓ2 Pearson criterion was used to evaluate the associations of alleles of selected genes with the risk of osteoporosis.Results and discussions. Analysis of the maps of 669 patients showed that for residents of the Russian Federation, the polymorphism rs3736228 of the LRP5 gene can be used as a genetic marker of osteoporosis, since there were significant differences in the frequency of occurrence of CT and TT allele variants in the group of patients with osteoporosis and in the control group. Results of studies of single-nucleotide polymorphisms COL1A1_rs1800012_G/T, CYP2R1_rs10741657_A/G, ESR1_rs2234693_C/T, ESR1_rs9340799_A/G, LCT_rs4988235_C/T, VDR_rs1544410_A/G, VDR_rs2228570_C/T in residents of the Russian Federation The federations did not show significant differences between the groups, therefore, in the future, the results of studies of these polymorphisms to assess the risk of osteoporosis in patients should be evaluated with caution.Conclusions. According to the results of the study conducted on residents of the Russian Federation, only one of the eight alleles in candidate genes for the risk of osteoporosis showed a significant relationship in patients in the Russian Federation. It has been shown that variants of TT and CT polymorphism rs3736228 of the LRP5 gene are the risk genotype for osteoporosis.

Single nucleotide polymorphism, haplotypes and genotypes of Mannose-binding lectin (MBL1) gene and their association with clinical mastitis in Murrah buffalo

The Mannose-binding lectin (MBL1) gene is an important component of immune response system. It plays vital role in activation of the complement system and act as chief defense molecule of host cell to provide protection against various diseases. In the recent study, six novel single nucleotide polymorphisms (SNPs), at 2689G&gt;C, 2751A&gt;G, 4822T&gt;C, 4853A&gt;G, 4855T&gt;C, and 4978T&gt;C resulted in 2 non synonymous type of change at 4853A&gt;G, 4855T&gt;C resulting in one amino acid substitution Ser150Gly of MBL1 protein and their association with clinical mastitis were investigated in two hundred (200) Murrah buffaloes. These SNPs in MBL1 were genotyped by using the polymerase chain reaction (PCR) and Deoxyribose nucleic acid (DNA) sequencing methods in order to reveal the association with clinical mastitis. SHEsis software tool was used for construction of haplotypes and Linkage disequilibrium analysis. Twenty one (21) haplotypes were constructed. Allelic association analysis showed that C allele of 2689 G&gt;C, A allele of 2751 A&gt;G, C allele of 4822 T&gt;C, A allele of 4853 A&gt;G, C allele of 4855 T&gt;C, and C allele of 4978 T&gt;C had significant association with increased risk of clinical mastitis in Murrah buffaloes (P&lt;0.05). Murrah buffaloes with CG genotype of 2689 G&gt;C, AG or GG genotype of 2751 A&gt;G, CC genotype of 4822T&gt;C, AG or GG genotype of 4853 A&gt;G, TC or CC genotype of 4855 T&gt;C and CC genotype of 4978 T&gt;C loci had significantly lower incidence of clinical mastitis compared to their counter genotypes. Haplotype association analysis showed that Hap21 (TATTGA) was found significantly related to higher risk of clinical mastitis (P&lt;0.05). Hap14 (TGTTGG) and Hap5 (CGCCCA) were found significantly associated with lower risk of clinical mastitis in Murrah buffalo (P&lt;0.05).