Polymorphism of the <i>VEGFA</i> (rs2010963) gene and low-dose exposure to airborne nickel as modification factors of programmed cell death in the Far North residents
Aug 2026· Hygiene and Sanitation· 0 citations· 14 references
TL;DR
Exposure to airborne nickel in the average daily dose, combined with the minor C-allele and CC-genotype of the VEGFA induces changes in indices of cell death and the immune profile in adults in the Far North (declining AnnexinV-FITC+7AAD– levels, growing levels of VEGF and IgE to nickel).
Abstract
Introduction. Special relevance should be assigned to investigating a phenomenon of programmed cell death in working age population in the Far North exposed to airborne metals and sub-Arctic climate, with gene polymorphism taken into account.Materials and methods. We examined adult participants (aged 21–59 years) who lived on territories with subarctic and continental type of climate with different levels of exposure to airborne nickel (n=525). Nickel levels were identified in blood using inductively coupled plasma mass spectrometry; cell death indicators AnnexinV-FITC+7AAD– and AnnexinV-FITC+7AAD+ – were established with flow cytometry; vascular endothelial growth factor VEGF, immune enzyme assay; IgE to nickel, allergosorbent tests; VEGFA (rs2010963) gene polymorphism, real-time PCR.Results. The immune profile in adults living in the Far North under low-dose exposure to airborne nickel (1.36 ∙ 10-³ mg/(kg ∙ day); 0.12 average daily MPC) and with resulting nickel in blood (0.0123±0.0015 µg/cm³) was characterized with excess levels of AnnexinV-FITC+7AAD+ (R²=0.404–0.503; p=0.029–0.042) and IgE to nickel (R²=0.613; p=0.001). However, exposure to airborne nickel in sub-Arctic climate leads to relative risk RR=1.19 (1.03–1.36); p=0.005) for apoptosis inhibition per the level of AnnexinV-FITC+7AAD– (R²=0.723–0.786; p=0.001–0.016). This risk is associated with the minor C-allele and CC-genotype of the VEGFA (rs2010963) (OR=1.91 (1.03–3.55)–2.93 (1.31–6.57).Limitations. The reference group samples are limited; the results should be verified in future research Conclusion. Exposure to airborne nickel in the average daily dose of 1.36 ∙ 10–³ mg/(kg ∙ day), combined with the minor C-allele and CC-genotype of the VEGFA (rs2010963) induces changes in indices of cell death and the immune profile in adults in the Far North (declining AnnexinV-FITC+7AAD– levels, growing levels of VEGF and IgE to nickel). These genetic and immunological indices can be recommended as key ones in pre-nosologic diagnostics and disease prevention in the far North population. Compliance with ethical standards. The study was accomplished in conformity with ethical standards stipulated by the Declaration of Helsinki and approved by the local ethics committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (Meeting Report No. 4 dated April 20, 2025). All participants gave informed voluntary written consent to participate in the study.Contributions: Zaitseva N.V. – study concept and design; Nikonoshina N.А. – data collection and analysis, writing the text; Dolgikh О.V. – study concept and design, editing the text; Alikina I.N., Kazakova О.А. – immunogenetic studies; Chigvintsev V.М. – mathematical modeling. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.Conflict of interest. The authors declare no conflict of interest.Funding. The study had no sponsorship.Received: May 18, 2026 / Accepted: July 1, 2026 / Published: August 14, 2026
Objective: We examined the correlation between functional polymorphisms in the high-affinity IgE receptor alpha chain gene (FCER1A), serum interleukin-6 (IL-6) concentrations, and the risk of RSA. Method: This case-control research comprised 185 women with idiopathic recurrent pregnancy loss (≥2 successive pregnancy losses) and 190 ethnically matched controls who had successful pregnancies. Genotyping of FCER1A polymorphisms (rs2251746). Serum IL-6 concentrations were quantified using ELISA. Relationships among genotypes, IL-6 concentrations, and clinical attributes were examined. Results: The FCER1A rs2251746 T allele exhibited a significant association with heightened RSA risk (OR=2.37, 95% CI: 1.69-3.31, p<0.001). The heterozygous (CT) and homozygous (TT) genotypes gave a 2.40-fold and 4.80-fold higher risk, respectively. Serum IL-6 concentrations were markedly increased in RSA patients relative to controls (6.84±2.31 vs. 3.62±1.47 pg/mL, p<0.0015). Genotypes Rs2251746 exhibited a significant correlation with IL-6 levels, demonstrating a steady increase from CC to TT genotypes in both RSA patients (p<0.0019) and controls (p=0.0072). In RSA patients, the TT genotype correlated with an increased incidence of pregnancy losses (p=0.0063) and an earlier gestational age at loss (p=0.0012) relative to other genotypes. Novelty: This offers fresh insights into the immunogenetic foundation of RSA and may reveal potential targets for therapeutic intervention in at-risk women.
Nawres Adnan Abdulameer, I. B. Amara· Journal for Technology and S...· 0 citations
Background: Immune modulation is central to cutaneous melanoma, and antitumor immune responses may be influenced by host genetic background. This study investigated the association between the interleukin-1β gene (IL1B) exon 5 synonymous single-nucleotide polymorphism rs1143634 (+3954 C>T) and cutaneous melanoma in a Northeast Italian case–control cohort. Methods: The study included 133 Caucasian patients with cutaneous melanoma and 945 healthy controls from Northeast Italy. The rs1143634 polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). Results: Compared with healthy controls, melanoma patients showed higher frequencies of the rs1143634 T allele [27.8% vs. 20.3%; odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.13–2.03, p = 0.005] and CT genotype (43.6% vs. 31.6%; OR = 1.67, CI = 1.16–2.42, p = 0.006), whereas the CC genotype was less frequent (50.4% vs. 63.9%; OR = 0.57, CI = 0.40–0.83, p = 0.003). TT + CT genotypes were more frequent among non-metastatic melanoma cases than controls (OR = 2.23, CI = 1.37–3.64, p = 0.001), but the direct comparison between metastatic and non-metastatic cases was not statistically significant. Among melanoma patients, TT + CT carriers showed an inverse association with Stage IV disease (OR = 0.38, CI = 0.15–0.94, p = 0.036) and a positive association with upper-limb melanoma (OR = 9.10, CI = 1.11–75.0, p = 0.040); these subgroup findings were exploratory because of small numbers and wide confidence intervals. Conclusions: These preliminary findings suggest a possible association between IL1B rs1143634 T allele carriage and cutaneous melanoma susceptibility in this cohort. The Stage IV and upper-limb observations should be considered hypothesis-generating. Larger independent studies, correction-aware statistical designs, cytokine or expression measurements, and functional validation are needed to confirm these observations and clarify their biological relevance.
S. Cauci, C. Buligan, Luca Bazzichetto et al.· Genes· 1 citation
Prostate cancer (PCa) is the second most common cancer among men worldwide. Immunological biomarkers play a crucial role in disease diagnosis, progression, and treatment. This study aimed to investigate the relationship between the rs5742621 (A>G) genetic variant and serum levels of insulin-like growth factor 1 (IGF-1) and other cytokines in patients with PCa compared to healthy controls. A total of 204 patients with PCa (aged 48–80) and 196 healthy controls were enrolled. Blood samples were collected to genotype the rs5742621 variant using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Serum levels of IGF1, macrophage migration inhibitory factor (MIF), CXC motif chemokine ligand 12 (CXCL12), and interleukin-27 (IL-27) were measured using a sandwich immunoassay. The heterozygous GA genotype of rs5742621 was more prevalent among patients with PCa, while the AA genotype was more prevalent in healthy controls. Additionally, serum IGF-1 levels were significantly elevated in PCa patients (median: 110 pg/mL) compared to healthy controls (median: 65 pg/mL; p < 0.001). Similarly, MIF levels were higher in PCa patients (85 pg/mL vs. 45 pg/mL; p < 0.001), as were CXCL12 concentrations (140 pg/mL vs. 40 pg/mL; p < 0.001). In contrast, IL-27 levels were lower in PCa patients (40 pg/mL) than in controls (65 pg/mL; p < 0.001). ROC curve analysis demonstrated that CXCL12 and MIF both achieved perfect diagnostic accuracy (AUC = 1.0), while IGF1 showed excellent diagnostic performance (AUC = 0.979) and IL-27 showed good performance (AUC = 0.903). The GA genotype of rs5742621 was significantly associated with elevated IGF-1 levels and increased PCa risk, promoting cell proliferation, inhibiting apoptosis, and accelerating tumor growth. IGF-1 and related immunological markers may serve as promising diagnostic biomarkers and potential therapeutic targets for prostate cancer.
Fatima Abdul Jabbar, R. AlChalabi, Russul AlObaidi et al.· Iraqi Journal of Science· 0 citations
Background
Interleukin-17A (IL-17A), encoded by the IL-17A gene on chromosome 6p12, is a pro-inflammatory cytokine that
plays a crucial role in immune regulation, inflammation, and carcinogenesis. The rs2275913 (G>A) polymorphism in
the promoter region of the IL-17A gene has been implicated in susceptibility to various inflammatory and malignant
conditions, including oral cancer. Oral squamous cell carcinoma represents one of the most common malignancies
worldwide, and genetic predisposition may contribute to its development.
Aim
To determine the genotype and allele frequencies of IL-17A gene polymorphism (rs2275913) and to evaluate its
association with susceptibility to oral cancer in a South Indian population.
Materials and Methods
A case-control study was conducted including 50 participants (25 oral cancer cases and 25 healthy controls). Genomic
DNA was extracted from peripheral blood samples and genotyping was performed using PCR-RFLP analysis. The
amplified product size was 102 bp, with digestion patterns identifying AA (102 bp), AG (68 + 34 bp), and GG (102 +
68 + 34 bp) genotypes. Statistical analysis was carried out using the Chi-square test, and Hardy–Weinberg equilibrium
(HWE) was assessed.
Results
Among cases, the genotype distribution was AA (28%), AG (24%), and GG (48%), while in controls it was AA (24%),
AG (20%), and GG (56%). The allele frequencies in cases were A (0.40) and G (0.60), and in controls were A (0.44)
and G (0.56). No statistically significant association was observed between IL-17A rs2275913 polymorphism and oral
cancer susceptibility (p > 0.05). Allele frequencies were comparable to those reported in the South Indian population.
Conclusion
The present study found no significant association between IL-17A rs2275913 polymorphism and oral cancer risk in
the studied South Indian population. Although genotype distributions were assessed with respect to HWE, larger
sample sizes are required to draw definitive conclusions regarding the role of this polymorphism in oral
carcinogenesis.
Uma Maheswari K, V. Priyadharshini, A. Ramasubramanian et al.· International Journal of Dru...· 0 citations
Background : Iron deficiency anemia (IDA) continues to pose a significant global health problem affecting diverse demographic groups worldwide. A complex interplay between environmental and genetic factors affects the development of IDA. In this context, Variation in TMPRSS6 gene has been identified as a potential risk factor. This study examines the association between TMPRSS6 rs1421312 SNPs and key biomarkers of iron deficiency status. These included hepcidin, soluble Transferrin Receptor Type 1 (sTfR1), and the sTfR1-F Index, among non-pregnant women of reproductive age. Methodology : To explore these associations, a cross-sectional design was employed. A total of 140 non-pregnant women, aged 17-50 years, were recruited based on low MCV and MCH. Participants were grouped into 60 IDA cases and 80 non-IDA cases based on a comprehensive analysis of their complete blood counts and serum iron studies. Additionally, DNA extraction and genotyping were carried out using allele-specific primers through PCR. Result: The distribution of genotypes for TMPRSS6 rs1421312 in cases without IDA (non-IDA) was 9(11.25%) (CC), 67(83.75%) (TC), and 4(5%) (TT). Whereas in cases with IDA, it was 8(13.33%) (CC), 48(80%) (TC), and 4(6.66%) (TT). No significant difference was found between the groups (P = 0.840). Additionally, the results indicated that the variations in Hepcidin levels, sTfR1, and the sTfR1-Ferritin Index among the CC, TT, and TC genotypes were not statistically significant. Conclusion: To the best of our knowledge, this represents the first such report from an Iraqi population. The current study concluded that no detectable association was found between the TMPRSS6 rs1421312 SNP and IDA. Additionally, no detectable associations were found with Hepcidin levels, sTfR1, or the sTfR1-Ferritin Index. Further studies are recommended to focus on the role of this SNP in IDA
D. Akbar, Hasan Al-Jaf, Ammar Lateef et al.· passer of basic and applied...· 0 citations
Simple Summary We determined the genotype and allele frequencies of the interleukin-1β gene (IL-1B) promoter polymorphism rs16944 (-511, C > T) in cutaneous melanoma patients and healthy controls from Northeastern Italy, a region with a high incidence of melanoma. The CC genotype and C allele were more frequent in melanoma cases than in healthy controls. Among melanoma patients, the CC genotype was more frequent in Stage I disease and in melanomas with Breslow thickness ≤ 0.75 mm, but less frequent in Stage IV melanoma. The CT genotype was associated with approximately 3-fold higher odds of Stage IV disease and approximately 2- to 3-fold higher odds of lower-limb or lower-extremity melanoma, including after multivariable adjustment. Thus, rs16944 emerged as a possible candidate marker associated with melanoma susceptibility, Stage IV status, and lower-extremity localization. Independent studies are required to confirm these preliminary, exploratory findings.
S. Cauci, C. Buligan, Patrizia Nacci et al.· Current Oncology· 0 citations
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
MIT News · Artificial Intelligence· news.mit.eduAug 17, 2026
