Association Of Polymorphisms Research Articles

Polymorphisms of the collagen genes of the fibrous ring rs1800012, rs2276454, rs1793953, and the VDR gene rs2228570 with intervertebral disc degeneration

Background. Spinal diseases cause significant disability, with genetic factors influencing up to 70 % of cases. This study purposed to examine the association of polymorphisms of COL1A1rs1800012, COL2A1rs2276454, COL2A1rs1793953 (collagen genes), and VDRrs2228570 with L4-L5, L5-S1, C5-C7 with intervertebral disc degeneration among ethnic Ukrainians. Materials and methods. The study included 90 individuals with L5-S1 disc degeneration, 50 — with L4-L5 degeneration, 30 — with C5-C7, and 66 controls without disc degeneration. Applied Biosystems (USA) kits were used for genotyping. Statistical analysis was performed using SNPStats. Results. There was an association between the C/C genotype and L5-S1 disc degeneration in men (odd ratio (OR) was 2.255, 95% confidence interval (CI): 1.089–4.670; χ2 = 4.905; p = 0.027), whereas the C/T genotype may have a protective effect (OR = 0.418, 95% CІ: 0.217–0.802; χ2 = 6.689, p = 0.009). The C/T genotype may also have protective significance for C5-C7 disc degeneration in men: its occurrence was higher among men in the control group compared to women (OR = 3.85, 95% CІ: 1.086–13.648; χ2 = 4.67; p = 0.031). The G/A COL2A1rs2276454 variant may have a protective effect on the L5-S1 disc (OR = 3.50, 95% CІ: 1.26–9.72; χ2 = 6.02; p = 0.015). The pair of alleles COL2A1rs2276454/COL2A1rs1793953 were linked to degenerative changes of the L4-L5 disc in the case group (p = 0.001); COL1A1rs1800012/VDRrs2228570 and COL2A1rs1793953/VDRrs2228570 were linked to degenerative changes in the C5-C7 disc. Conclusions. The C/C VDRrs2228570 genotype in men was associated with L5-S1 intervertebral disc degeneration. The T/C VDRrs2228570 genotype may have a protective significance for men with L5-S1 and C5-C7 degeneration. The COL2A1rs2276454 variant may have a protective effect against the development of L5-S1 degenerative changes in men. The allele pairs COL1A1rs1800012/VDRrs2228570, COL2A1rs1793953/VDRrs2228570, and COL2A1rs2276454/COL2A1rs1793953 were associated with C5-C7 degeneration, while the COL2A1rs2276454/COL2A1rs1793953 pair were associated with L4-L5 degeneration.

Association of prolactin gene polymorphism with milk production traits in Gaolao cattle

Association of prolactin gene polymorphism with milk production traits in Gaolao cattle

Association of single nucleotide polymorphisms in Neuropeptide Y (NPY) and Phosphoglycerate Mutase 2 (PGAM2) genes with growth traits in rabbits

Genetic improvement of local rabbit breeds using modern approaches such as marker-assisted selection requires accurate and precise information about marker‒trait associations in animals with different genetic backgrounds. Therefore, this study was designed to estimate the association between two mutations located in the Neuropeptide Y (NPY, g.1778G > C) and Phosphoglycerate Mutase 2 (PGAM2, c.195 C > T) genes in New Zealand White (NZW), Baladi (BR), and V-line rabbits. The first mutation was genotyped using high-resolution melting, and the second mutation was genotyped using the PCR-RFLP method. The results revealed significant associations between the NPY mutation and body weight at 10 (V-line) and 12 weeks of age (NZW, BR, and V-line), body weight gain (BWG) from 10 to 12 weeks of age (BR), BWG from 6 to 12 weeks of age (NZW, BR, and V-line), average daily gain (NZW, BR, and V-line, and BR), growth rate (GR) from 8 to10 weeks (V-line), 10 to 12 weeks (BR), and GR from 6 to 12 weeks of age (BR, and V-line). The PGAM2 mutation was associated with body weight at 10 (V-line) and 12 (NZW, and V-line) weeks of age, with significant positive additive effects at 12 weeks of age in all breeds, and was associated with BWG from 8 to 10 and 10 to 12 in BR, and BWG from 6 to 12 weeks of age (NZW, and BR), and average daily gain (NZW, and BR), and was associated with GR form 8 to 10 weeks (BR), from10 to 12 weeks (BR, and V-line) and from 6 to 12 weeks (BR). The results highlighted the importance of the two mutations in growth development, and the possibility of considering them as candidate genes for late growth in rabbits.

Association of CTLA-4 gene polymorphisms with the genetic susceptibility and prognosis of patients with Bladder urothelial carcinoma

To assess the association of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC). From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group (n = 166) and poor prognosis group (n = 86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis. No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups (P > 0.05). The frequencies of GG genotype and G allele for the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group (P < 0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups (P > 0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group (P < 0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P < 0.001). The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.

Association of VEGFR1, VEGFR2 and VEGFR3 polymorphisms with esophageal cancer risk: a case–control study

BackgroundEsophageal cancer is the eleventh most common cancer and is the seventh leading cause of mortality worldwide. Vascular endothelial growth factor (VEGF) and its receptors pathway are a key regulator of angiogenesis and play an important role in carcinogenesis. The aim of current study was to evaluate the association of five VEGFR polymorphisms with esophageal cancer risk in patients from Punjab, North-west India.MethodsThis case–control study included 310 esophageal cancer patients and 325 age and gender matched healthy controls. VEGFR1-710C/T, VEGFR2-604 T/C (rs2071559), VEGFR2 1192 G/A (rs2305948), VEGFR2 1719A/T (rs1870377) and VEGFR3 (rs72816988) polymorphisms were genotyped by using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Restriction digestion products were analyzed on 2.4% agarose gel and genotype was assigned to each sample on the basis of fragments obtained after digestion. Randomly 10% samples were repeated by Sanger sequencing to revalidate the results.ResultsThere was a significant association of CT genotype (OR = 0.28; 95%CI, 0.10–0.76; p = 0.01) and T allele (OR = 0.28; 95%CI, 0.10–0.77; p = 0.01) of VEGFR1-710C/T polymorphism with decreased risk of esophageal cancer. TC genotype of VEGFR2-604 T/C (OR = 0.66; 95%CI, 0.44–0.97; p = 0.03) and GA genotype of VEGFR2 1192G/A (OR = 0.54; 95%CI, 0.31–0.95; p = 0.03) polymorphisms were significantly associated with decreased risk of esophageal cancer. There was no significant difference in allele and genotype frequency of VEGFR2 1719A/T and VEGFR3 (rs72816988) polymorphisms between esophageal cancer patients and controls (p > 0.05). Haplotype analysis revealed that haplotype C-604A1719A1192 was significantly associated with the decreased esophageal cancer risk (OR = 0.44; 95%CI, 0.23–0.84; p = 0.01).ConclusionVEGFR1-710C/T, VEGFR2-604 T/C and VEGFR2 1192G/A polymorphisms were associated with the decreased risk of esophageal cancer in patients from Punjab, North-west India.Graphical abstract

Association of CETP Gene Polymorphisms and Haplotypes with Acute Heart Rate Response to Exercise.

Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624-Cdominant: B = -8.41, p < 0.001; rs708272-Gdominant: B = -8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-Cdominant: OR = 0.44, p = 0.004; rs708272-Gdominant: OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3-CAGCA: B = -6.81, p = 0.003; H9-CGGCG: B = -14.64, p = 0.015) and lower risk of adverse AHRR (H3-CAGCA: OR = 0.58, p = 0.040; H9-CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1-AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile.

22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)

Abstract Background Adverse events (AEs) can limit treatment immune checkpoint inhibitors (ICI) efficacy and worsen patient outcomes. Our group recently identified a germline IL7 SNP as a potential biomarker for prediction of irAEs (Groha, Nat Med 2022). In the current study, we sought to replicate the association between this IL7 SNP (rs16906115) and AEs in two clinical trials of patients with cancer treated with ICI regimens. Methods In the CheckMate-025 (CM025) trial (NCT01668784), involving patients with metastatic renal cell carcinoma (mRCC) randomized to either nivolumab (NIVO) or everolimus (EVE), whole-exome sequencing (WES) data from tumor and peripheral blood samples were analyzed. The Cancer Genome Analysis pipeline was utilized to identify somatic alterations, and the STITCH pipeline was employed to determine SNP carrier status. In the BinTA-0037 (BTA-0037) trial (NCT03631706), focusing on patients with metastatic non-small cell lung cancer (mNSCLC), the carrier status of a surrogate SNP rs16906062 (R2=0.66) was determined from tumor WES in the pembrolizumab (PEMBRO) arm. Within each treatment arm, time to incident AEs were compared between carriers (SNP+) and non-carriers (SNP-) via multivariable Cox regression, controlling for age, sex, race, ECOG and sample purity. A SNP´treatment interaction term was also included in the entire CM025 cohort. Censoring for AEs occurred at death or last follow-up. A recurrent event analysis for AEs was conducted using the Andersen-Gill model, controlling for the same variables. Additionally, overall survival (OS) and progression-free survival (PFS) were also assessed. Results In total, 534 pts were included (NIVO: n=189, PEMBRO: n=152, EVE: n=193), among which 82 (15.4%) were SNP+. There were no differences in clinical and pathological characteristics between SNP+ and SNP-, except for sex (SNP+ 16.1% vs. SNP- 30.1% in females, P=0.046). Similarly, no differences in somatic alterations, including single nucleotide and copy number variants were seen between SNP+ and SNP- in CM025. SNP carrier status had no effect on OS nor PFS in all treatment arms (all P≥0.22). The rate of grade 2+ AEs was significantly higher in SNP+ vs. SNP- in the NIVO arm (Figure A, HR=2.91[1.48-5.72]), but not in the EVE (Figure B, control, non-ICI) arm (HR=0.63[0.3-1.29], SNP´treatment Pinteraction=0.002). Similarly, the rate of all grade AEs in the PEMBRO arm of BTA-0037 was higher in SNP+ vs. SNP- (Figure C, HR=2.30[1.60-4.60]). The rate of recurrent grade 2+ AEs was also significantly higher in SNP+ vs. SNP- in the NIVO arm (HR=3.43[1.83-6.43]), whereas a trend for fewer recurrent grade 2+ AEs was seen in SNP+ vs. SNP- in the EVE arm (HR=0.46[0.17-1.25], SNP´treatment Pinteraction=0.0005). Figure: Kaplan-Meier curves showing the cumulative rate of adverse events in the NIVO (A) and EVE (B) arms of CM025, as well as the PEMBRO arm of BTA0037 (C), in SNP- and SNP+. Conclusions The IL7 SNP (rs16906115) is associated with significantly higher rates of grade 2+ AEs, including recurrent events, in pts with mRCC or mNSCLC treated with single agent PD-1 inhibitors but not with non-ICI regimens, with no effect on survival and efficacy outcomes. These results confirm the SNP’s predictive potential as a biomarker for irAEs to guide therapeutic decisions in pts treated with ICIs.

Association of VEGFA polymorphisms with the risk of oesophageal cancer in Punjab, India: A case-control study.

Background & objectives Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors which stimulates tumour progression induction of endothelial cell migration and division, inhibition of the apoptosis of endothelial cells, induction of serine protease activity and enhancement of vascular permeability. This study aimed to investigate the correlation of VEGF+405G/C,-7C/T and+936C/T polymorphisms with oesophageal cancer risk. Methods DNA samples of 464 subjects (231 sporadic oesophageal cancer affected individuals and 233 controls) were genotyped forVEGF+936C/T,+405G/C and-7C/T polymorphisms. VEGF+936C/T and +405G/C polymorphisms were genotyped by PCR-RFLP method whereas VEGF-7C/T polymorphism was genotyped using Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results CT genotype of VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer. VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer underdominant, co-dominant, over dominant and log-additive genetic models in total patients and in the female group. C+936G+405T-7 haplotype was significantly associated with decreased risk (P=0.01)of oesophageal cancer in total patients and also in the male group (P=0.02). Interpretation & conclusions In future, replication of the findings of the present study in a larger sample from different ethnic groups, along with functional analysis, may be insightful for the role of VEGFA polymorphisms in the pathogenesis of oesophageal cancer. Identification of the correlation of VEGF variants with specific therapy in oesophageal cancer may help in better selection of patients and monitoring treatment response in VEGF-therapy.

IL-10 -592 C/A polymorphism association with hemorrhagic stroke/aneurysm and their risk factors

IL-10 -592 C/A polymorphism association with hemorrhagic stroke/aneurysm and their risk factors

Single Nucleotide Polymorphisms in APE1, hOGG1, RAD51 Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients.

Radiotherapy (RT) is a crucial treatment for head and neck cancer however, it causes adverse reactions to the normal tissue and organs adjacent to target tumor. The present study was carried out to investigate possible association of single nucleotide polymorphism in DNA repair genes with toxicity effects of radiotherapy on normal tissue. Three hundred and fifty head and neck cancer patients receiving radiotherapy treatment were enrolled in this study. The adverse after effects of radiotherapy on the normal tissue in the form of skin reactions were recorded. Single nucleotide polymorphisms of APE1 (rs1130409), hOGG1 (rs1052133) and Rad51 (rs1801320, rs1801321) genes were studied by polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing methods and their association with development of severe radio-toxicity effects was evaluated logistic regression analysis. The 172G/T polymorphism of Rad51 was 2.85 times higher and significantly associated with skin reactions (OR=2.85, 95% CI: 1.50-5.41; p=0.001) and severe oral mucositis (OR=4.96, 95% CI: 2.40-10.25; p<0.0001). These results suggested that the polymorphic nature of Rad51 is responsible for risk of radiotherapy adverse effects in HNC patients. The variant 326Cys and heterozygous 326Ser/Cys genotype of hOGG1 was significantly associated with high tumor grade (OR=3.16 95% CI: 1.66-5.99; p=0.0004, and OR=3.97 95% CI: 2.15-7.34; p=<0.0001 respectively). The homozygous variant 172TT genotype of Rad51 showed positive association with poor response of both tumor and nodes towards radiotherapy treatment (p=0.007 and p=0.022). Interpretation of our results revealed significant association of rs1801321 SNP of Rad51 with development of adverse toxicity reactions in normal tissue of head and neck cancer patients treated with radiotherapy.

Association of Single Nucleotide Polymorphism in OCT1 and OCT3 Genes with the Efficacy of Metformin Response in North Indian Type 2 Diabetes Mellitus Patients

Introduction: Variability in the effectiveness of metformin treatment among individuals with type 2 diabetes mellitus (T2DM) has been linked to various genetic factors. Understanding the genetic mechanisms underlying the action of metformin can greatly aid the personalized management of T2DM. Our investigation aimed to explore the impact of genetic variations in the organic cation transporters (OCT1 and OCT3) genes on the efficacy of metformin therapy in T2DM individuals from North India. Methods: This observational cross-sectional study assessed the influence of OCT1 (rs628031) and OCT3 (rs2292334) polymorphisms on metformin response in T2DM patients. Metformin response was determined based on HbA1c levels, dividing patients (n = 177) into two categories: responders (HbA1C&lt;7%; n = 127) and non-responders (HbA1C≥7%; n = 50). Responders were further classified as T2DM patients receiving either monotherapy (n = 55) or combination therapy (n = 72). Genotyping was conducted using the PCR-RFLP method. Results: No significant association was observed between OCT1 (rs628031) polymorphism and metformin response in T2DM patients. However, a notable association was found between OCT3 (rs2292334) polymorphism and metformin response. Carriers of the AA genotype exhibited enhanced efficacy of metformin in both monotherapy (OR (CI)= 0.29(0.11-0.72), p=0.007) and combination therapy (OR (CI)= 0.41(0.16-1.0), p=0.047). Additionally, the A allele was more prevalent in responders (OR (CI)= 0.48(0.28-0.84), p=0.010), while the G allele was associated with reduced efficacy of metformin in T2DM patients (OR (CI)= 2.07(1.19-3.61), p=0.010). Conclusion: Genotyping of OCT3 (rs2292334) may serve as a valuable tool in predicting the response to metformin in T2DM patients.

Association of IL-17A and IL-10 Polymorphisms with Juvenile Idiopathic Arthritis in Finnish Children.

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

Genetic variants in the TNF pathway impact TNFi response in a mixed population with rheumatoid arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies.

Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real-life clinical practice.

Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.

Association of rs4588 polymorphism in vitamin D binding protein gene with polycystic ovarian syndrome in Iranian women: a case-control study

ObjectiveVitamin D deficiency and variations in the vitamin D binding protein (VDBP) gene may play a role in the development of Polycystic ovary syndrome (PCOS). This study aims to investigate the association of the rs4588 polymorphism with PCOS in Iranian women, as well as its association with infertility and recurrent pregnancy loss (RPL) in these patients.ResultsThe analysis revealed statistically significant differences in the distributions of genotypes and alleles of the rs4588 polymorphism among the three groups (p < 0.0001). The AC genotype and A allele showed an association with an elevated risk of PCOS and infertility. In this study, no association was found between genotypes and alleles of the rs4588 polymorphism and the risk of RPL in women with PCOS. Subjects with the AA or AC genotype exhibited significantly higher levels of LDL compared to those with the CC genotype.

Exploring WNT2 polymorphisms in comitant strabismus: A genetic association study

BackgroundStrabismus is a complex oculomotor condition characterized by a misalignment of the visual axis. The genetics of strabismus are poorly defined although a few candidate genes have been identified, among which is the WNT2 gene. Our study was designed to assess the association of single nucleotide polymorphisms (SNPs) of WNT2 in Pakistani strabismus patients. MethodsA total of six SNPs, three intronic and three in the 3́ untranslated region, were screened in the current study. Logistic regression was performed using a dominant, recessive and additive model to determine the association of SNPs with strabismus and its clinical subtypes: esotropia and exotropia. Furthermore, haplotype analysis was performed. ResultsRegression analysis revealed an association of rs2896218, rs3779550, rs2285544 and rs4730775 with strabismus under the dominant model. When analyzed separately, rs2896218 and rs2285544 were found to be associated with both esotropia and exotropia, while rs4730775 was significantly associated only with exotropia under the dominant model. Based on clinical parameters, rs2896218, rs2285544 and rs4730775 were also found to be associated with the group of strabismus patients who were diagnosed at birth, but not in the group of patients who were diagnosed later in life. Haplotype analysis revealed that the haplotype A T T (corresponding to rs2896218, rs3779550 and rs2285544) was significantly more prevalent in the strabismus group. ConclusionOverall, the results of the present study suggest an association of WNT2 polymorphisms with strabismus and its subtypes in the Pakistani population, though further studies are needed to elucidate their role in strabismus etiology.

Integrative prediction model for radiation pneumonitis incorporating genetic and clinical-pathological factors using machine learning

PurposeWe aimed to develop a machine learning-based prediction model for severe radiation pneumonitis (RP) by integrating relevant clinicopathological and genetic factors, considering the associations of clinical, dosimetric parameters, and single nucleotide polymorphisms (SNPs) of genes in the TGF-β1 pathway with RP. MethodsWe prospectively enrolled 59 primary lung cancer patients undergoing radiotherapy and analyzed pretreatment blood samples, clinicopathological/dosimetric variables, and 11 functional SNPs in TGFβ pathway genes. Using the Synthetic Minority Over-sampling Technique (SMOTE) and nested cross-validation, we developed a machine learning-based prediction model for severe RP (grade ≥ 2). Feature selection was conducted using four methods (filtered-based, wrapper-based, embedded, and logistic regression), and performance was evaluated using three machine learning models. ResultsSevere RP occurred in 20.3 % of patients with a median follow-up of 39.7 months. In our final model, age (>66 years), smoking history, PTV volume (>300 cc), and AG/GG genotype in BMP2 rs1979855 were identified as the most significant predictors. Additionally, incorporating genomic variables for prediction alongside clinicopathological variables significantly improved the AUC compared to using clinicopathological variables alone (0.822 vs. 0.741, p = 0.029). The same feature set was selected using both the wrapper-based method and logistic model, demonstrating the best performance across all machine learning models (AUC: XGBoost 0.815, RF 0.805, SVM 0.712, respectively). ConclusionWe successfully developed a machine learning-based prediction model for RP, demonstrating age, smoking history, PTV volume, and BMP2 rs1979855 genotype as significant predictors. Notably, incorporating SNP data significantly enhanced predictive performance compared to clinicopathological factors alone.

Association of ACE2 and TMPRSS2 towards COVID-19 susceptibility

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) is pneumonia like viral disease which was originated from Wuhan China in 2019. Besides its high morbidity and mortality, a lot of physiological, enzymatic, hormonal and genetic imbalances had also been observed among Corona Virus Disease-19 (COVID-19) patients. The purpose of the present study was the assessment of comorbidities and association of single nucleotide polymorphisms (SNPs) in Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine (TMPRSS) gene among COVID-19 patients. A total of 300 (healthy control n = 150 COVID-19 n = 150) individuals were sampled and genotyped for ACE2 rs2285666 and TMPRSS rs2070788 SNPs respectively. A total of 92/150 (61.3%) were male infected population, among the various age groups (age group 1: 1–15 yrs; age group 2: 16–30 yrs; age group 3: 31–45; age group 4: 46 and above) where most of the patients were from age group 4 (46 and above) 79/150 (52.7%) followed by age group 3 (31–45) 44/150 (29.3%). Logistic regression analysis showed that among clinical features cough (90%) was observed to be highest followed by fever (80%), sore throat (76%) and shortness of breath (75%). Hypertension (51%), type II diabetes (48.4%), ischemic heart disease (43.3%) history was found to prevalent highly associated with infected individuals. For ACE2 rs2285666, we found disease risk association for both allele and genotype while TMPRSS did not reveal genotype association. It is concluded from the current study that COVID-19 infects majority of male population. ACE2 rs2285666 allele and genotype association was observed with COVID-19 infection and protective association of TMPRSS2 rs2070788 allele towards COVID-19 infection.

Association of TLR2 Arg753Gln gene polymorphism with its expression level in nonagenarians with frailty

Association of TLR2 Arg753Gln gene polymorphism with its expression level in nonagenarians with frailty

Exploring Gene Polymorphisms Associated with Otitis Media through Variable Number Tandem Repeats (VNTR) Region

Background: Otitis is an inflammation and infection of the inner lining of the middle ear. The problem known as suppurative otitis media if there are droplets and holes in the tympanic membrane due to this inflammation and infection of the mucous membrane. The present study focused on specific genes suspected to be associated with otitis media in 60 subjects clinically diagnosed with OM The study focuses on two genes, MUC5B and IL-1RN, whose genes mutations by variable number of tandem repeat (VNTR) regionsMethods: Variable numbers of tandem repeats (VNTR) regions were used to genotype 60 patients with otitis media and 30 healthy individuals for genotypic polymorphisms for the MUC5B and IL-1RN genes by number of tandem repeats (VNTR) regions on a variable basis Blood samples were collected from participants, and three milliliters were placed directly into EDTA tubes. Subsequently, PCR products were detected by agarose gel electrophoresis and visualized by ethidium bromide staining. The size of amplified DNA fragments was determined by comparison with a 100-bp DNA ladder molecule size markerResults: About the same, the paper represents the association of gene polymorphisms with otitis media by genotyping a total of 60 patients as OM, and, on the other hand, 30 individuals were noted to be healthy. This was to determine genotypic polymorphisms for the two genes, that is, MUC5B and IL1RN, within the VNTR region. The results showed that the carriers of allele 2 in the genotypic position had a risk of nearly twofold getting otitis media.Conclusion: Polymorphism of the MUC5B and IL-1RN genes can be responsible for the severity of the inflammatory process in the middle ear, complicated by otitis media or hearing loss.Keywords: Otitis media; Gene polymorphism; MUC5B; IL-1RN; VNTR