Search Results (56)

Background/Objectives: Arterial stiffness increases with progressive worsening of renal function and predicts cardiovascular mortality in patients with chronic kidney disease. The effects of vitamin K-dependent proteins in vascular health and the implications of vitamin K epoxide reductase gene (VKORC1) polymorphisms in calcification and warfarin sensitivity are well known, but their roles in arterial stiffness are not known. We investigated the influence of common polymorphisms in this gene (−1639G>A, +1173C>T, +1542G>C, +2255C>T, and +3730G>A) on stiffness and calcification markers in 302 CKD patients. Methods: Blood pressure, aortic pulse wave velocity (aPWV), coronary artery calcification (CAC), and aortic calcification (AC) were assessed together with the total uncarboxylated matrix Gla protein (t-uncMGP). Results: Genotyping subjects for +1542G>C and +3730G>A showed higher genotype-specific aPWV and lower t-uncMGP (p < 0.05). The combined recessive allele model showed a significant stepwise reduction in aPWV (p < 0.005); subjects homozygous for both risk alleles had the highest aPWV compared to those carrying one or none. In a multiple regression model adjusting for age, gender, mean pressure, BMI, and racial group, each +1542G allele and +3730A allele were independently associated with a 0.8 m/s (95% CI 0.09 to 1.57) and 1.0 m/s (95% CI 0.14 to 1.98) elevation of aPWV, respectively. Although serum t-uncMGP levels correlated inversely with CAC score (p < 0.001), VKORC1 genotypes did not. Conclusions: We demonstrated for the first time that VKORC1 polymorphisms (+1542G>C and +3730G>A) influence arterial stiffness and serum t-uncMGP levels in CKD patients. These findings suggest that vitamin K-dependent processes may be important in arterial stiffness, possibly by modulating calcification of the vessel wall. Full article

Background/Objectives: The gluten-free diet (GFD) may be anti-inflammatory in treating Hashimoto’s thyroiditis (HT), but the studies are inconsistent. Methods: To determine the effects of the GFD in non-celiac HT, we included randomized controlled trials from the following databases: Cochrane Central, Embase, Lilacs, Medline, Scopus, and Web of Science. The study was registered at Prospero (no. CRD42024566034). The outcomes assessed included free triiodothyronine (fT3), free tetraiodothyronine (fT4), thyroid stimulating hormone (TSH), Anti-thyroid Peroxidase (TPO), anti-thyroglobulin (Tg), C-reactive protein (CRP), body weight (BW), body mass index (BMI) and adverse effects. Sensitivity, subgroup, meta-regression, bias risk, and evidence analyses’ certainty were also assessed. Results: Only three studies were meta-analyzed, comprising 110 participants. The pooled data revealed the evidence was very uncertain about the effect of GFD compared to the control group on mean differences (MD) of TSH (MD −0.63 uIU/mL; 95% CI −1.63 to 0.36; p = 0.21), fT3 (MD −0.18 pg/mL; 95% CI −0.50 to 0.14; p = 0.28), fT4 (MD −0.33 ng/dL; 95% CI −0.89 to 0.23; p = 0.24), anti-Tg (MD −10.07 IU/mL; 95% CI −17.73 to −2.42; p = 0.010), anti-TPO (MD 76.19 IU/mL; 95% CI 46.86 to 108.51; p < 0.00001), CRP (MD −0.12 IU/mL; 95% CI −0.30 to 0.07), BW (MD −1.46 kg; 95% CI −6.70 to 3.77), and BMI (MD −1.80 kg/m2; 95% CI −3.30 to −0.31). The quality of evidence was rated as having serious methodological concerns to extremely serious imprecision. Conclusions: The GFD decreased anti-Tg and increased the anti-TPO levels, both significantly. There were no significant results on fT3, fT4, and TSH. Full article

Background/Objectives: History of gestational diabetes mellitus (GDM) is a strong risk factor in the development of type 2 diabetes (T2D). We sought to examine the association between perceived risk of developing T2D and relevant health behaviors in this population. Methods: We analyzed self-reported survey items and objective electronic health record data of participants in the Gestational diabetes Risk Attenuation for New Diabetes (GRAND) Study, a multisite randomized control trial testing the effectiveness of shared decision-making for women with elevated body mass index (BMI), prediabetes and history of GDM. Data on demographics, health behaviors, and perceived T2D risk were self-reported. We ran four regression models to study the association between women’s perceived risk of developing T2D and four key health behaviors: (1) physical activity, (2) consumption of sugar-sweetened beverages, (3) consumption of ultra-processed foods, and (4) consumption of meals prepared outside the home. All models were adjusted for age, race, ethnicity, income, HbA1c, BMI, family history of T2D, and study arm. Results: Our sample included 242 women who on average were 41 years old (±6 years) with BMI of 32.7 (±6.9 kg/m²). Perceived risk of developing T2D was not significantly associated with physical activity, consumption of sugar-sweetened beverages, ultra-processed food consumption, or meals prepared outside of the home. Higher BMI was significantly associated with increased consumption of sugar-sweetened beverages (OR 1.05, 95% CI 1.01–1.10), but not other health behaviors. Conclusions: We found perceived risk of developing T2D was not independently associated with four key health behaviors. Women with GDM are at high risk of developing T2D and may benefit from tailored or more intensive strategies promoting health behavior changes shown to lower T2D risk. Full article

Background/Objectives: Ultra-processed food consumption has been shown to be linked with clinical cardiovascular disease. This study aims to examine the associations of ultra-processed food consumption with biomarkers for subclinical-level myocardial damage [high-sensitivity cardiac troponin I and T (hs-cTnI and hs-cTnT)] and myocardial stretch (NT-proBNP) in U.S. adults. Methods: We used data from 6615 U.S. adults aged ≥20 years without prevalent cardiovascular disease from the National Health and Nutrition Examination Survey 2001–2004. We identified ultra-processed food by applying the Nova classification to dietary recall data, and we divided participants into quartiles based on their consumption, expressed as a proportion of total daily energy (%kcal) and gram intakes (%grams). We defined elevated cardiac biomarkers as hs-cTnI > 12 ng/L in men and >10 ng/L in women, hs-cTnT ≥ 14 ng/L for all participants, and NT-proBNP ≥ 125 pg/mL for age < 75 y and ≥450 pg/mL for age ≥ 75 y. We used multivariable logistic regression with adjustment for socio-demographic, total energy intake, behavioral, and clinical characteristics. Results: Higher ultra-processed food intake in %grams was associated with elevated NT-proBNP [odds ratio (OR) for quartile 4 vs. 1: 1.27, 95% CI: 1.00–1.61] when socio-demographic characteristics and total energy intake were adjusted for, but this was not the case with hs-cTnI or hs-cTnT. Further adjusting for clinical characteristics attenuated the association with NT-proBNP (OR: 1.26, 95% CI: 0.98, 1.61). There was no consistent association between ultra-processed food in %kcal and elevated NT-proBNP, hs-cTnT, or hs-cTnI. Conclusions: Ultra-processed food consumption is associated with subclinical myocardial stretch, a precursor to early heart failure. This supports the potential risks of subclinical cardiovascular disease associated with consuming ultra-processed food. Full article

Candida auris has emerged as a global public health threat due to its high mortality rates, multidrug resistance, and rapid transmission in healthcare settings. This study reports the first documented cases of C. auris candidemia in Portugal, comprising eight isolates from candidemia and colonised patients admitted to a major hospital in northern Portugal in 2023. Whole-genome sequencing (WGS) was performed to determine the phylogenetic relationships of the isolates, which were classified as belonging to Clade I. Genome sequencing also enabled the detection of missense mutations in antifungal resistance genes, which were correlated with antifungal susceptibility profiles determined according to EUCAST (European Committee on Antimicrobial Susceptibility Test) protocols and guidelines. All isolates exhibited resistance to fluconazole and amphotericin B according to the recently established EUCAST epidemiological cut-offs (ECOFFs). Most of the isolates showed a resistant phenotype to anidulafungin and micafungin. All isolates were resistant to caspofungin. Missense mutations identified included Y132F in ERG11, E709D in CDR1, A583S in TAC1b, K52N and E1464K in SNQ2, K74E in CIS2, M192I in ERG4, a novel mutation S237T in CRZ1, and variants in GCN5, a gene involved in chromatin remodelling and stress-response regulation. Identifying known and novel mutations highlights the evolution of antifungal resistance mechanisms in C. auris. These findings underscore the need for further research to understand C. auris resistance pathways and to guide effective clinical management strategies. Full article

Objectives: This study investigates the nonlinear association between myeloperoxidase (MPO) levels and Helicobacter pylori (H. pylori) infection risk in Chinese adults, evaluating potential modifiers and clinical implications for infection prevention. Methods: An analysis was conducted on cross-sectional data from 15,180 adults who underwent routine health examinations between January and December 2021. H. pylori infection was diagnosed using the 14C-urea breath test with a threshold of disintegrations per minute (DPM) ≥ 100. ELISA was used to measure plasma MPO levels. Nonlinear associations were assessed through logistic regression, restricted cubic splines, threshold effect analysis, and subgroup interactions. Results: The study identified a U-shaped correlation between MPO levels and the risk of H. pylori infection. Compared to the middle tertile (T2: 20.6–31 ng/mL), participants in the lowest (T1: ≤20.6 ng/mL; OR = 1.36, 95% CI: 1.24–1.49) and highest tertiles (T3: ≥31 ng/mL; OR = 1.12, 1.02–1.22) exhibited elevated infection risk after full adjustment (p < 0.001). DPM levels were notably elevated in T1 (β = 37.1, 26.66–47.57) and T3 (β = 19.27, 8.81–29.72) relative to T2 (p < 0.0001). RCS-based threshold analysis identified a nonlinear inflection at 24.0 ng/mL of MPO, where each additional 1 ng/mL of MPO below this threshold was associated with a reduced infection risk (OR = 0.959, 95% CI: 0.947–0.971), whereas levels above increased the risk (OR = 1.004, 95% CI: 1.002–1.007). This pattern aligned with H. pylori breath test values, which mirrored the U-shaped trend across MPO tertiles. Subgroup analyses revealed uniform associations between MPO and H. pylori infection risk/DPM across various factors such as age, sex, BMI, and metabolic comorbidities, with all interaction p-values exceeding 0.05. Conclusions: MPO levels exhibit a robust U-shaped association with H. pylori infection risk, independent of anthropometric and metabolic confounders. Monitoring MPO may aid in identifying individuals at bidirectional infection risk, suggesting novel insights into the inflammation–infection interplay. The study’s cross-sectional design limits the ability to establish causal relationships, necessitating further longitudinal research to validate these findings and elucidate their clinical implications. Full article

Objectives: Evaluation of the predictive potential of pre-CAR-T [¹⁸F]FDG PET/CT in Diffuse Large B-Cell Lymphoma (DLBCL) patients concerning Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS). Methods: Eighteen DLBCL patients (mean age: 60 ± 12 years) who underwent pre-therapeutic [¹⁸F]FDG-PET/CT and CAR-T cell therapy were retrospectively included. Median follow-up time was ten months (IQR6-16) after CAR-T cell infusion. Age, sex, serum lactate dehydrogenase (LDH), interleukin-6 (IL-6), C-reactive protein (CRP), and modified Endothelial Activation and Stress Index (mEASIX) were obtained. Potential occurrence of CRS/ICANS and the SUV_max were evaluated. Pearson and Spearman correlations, group comparisons (Mann–Whitney U-test) and the odds ratio (OR) were calculated. P values below 0.05 were defined as statistically significant and 95%-confidence intervals (CI) were calculated. Results: Pre-therapeutic SUV_max correlated positively with LDH (r = 0.5; p = 0.02), with the grade of CRS (r = 0.5; p = 0.03) and with the grade of ICANS (r = 0.6; p = 0.01). Appearance of ICANS was significantly correlated with pre-therapeutic SUV_max (p = 0.03; U = 7.0; Z = −2.2). Using ROC analysis and Youden’s index, an SUV_max threshold of 17 (AUC: 0.865; p < 0.01) was defined. Patients exceeding a pre-therapeutic SUV_max of 17 had a significantly higher risk of CRS grade > 1 (OR = 22; CI 2, 314; p = 0.03) and ICANS grade > 1 (OR = 18; CI 1, 271; p = 0.04). Conclusions: Pre-therapeutic SUV_max may be a useful marker for identifying DLBCL patients at risk for CRS and ICANS. Full article

Many speech coding strategies have been developed over the years, but comparing them has been convoluted due to the difficulty in disentangling brand-specific and patient-specific factors from strategy-specific factors that contribute to speech understanding. Here, we present a comparison with a ‘virtual’ patient, by comparing two strategies from two different manufacturers, Advanced Combination Encoder (ACE) versus HiResolution Fidelity 120 (F120), running on two different implant systems in a computational model with the same anatomy and neural properties. We fitted both strategies to an expected T-level and C- or M-level based on the spike rate for each electrode contact’s allocated frequency (center electrode frequency) of the respective array. This paper highlights neural and electrical differences due to brand-specific characteristics such as pulse rate/channel, recruitment of adjacent electrodes, and presence of subthreshold pulses or interphase gaps. These differences lead to considerably different recruitment patterns of nerve fibers, while achieving the same total spike rates, i.e., loudness percepts. Also, loudness growth curves differ significantly between brands. The model is able to demonstrate considerable electrical and neural differences in the way loudness growth is achieved in CIs from different manufacturers. Full article

Background/Objectives: Clozapine, the gold-standard treatment for treatment-resistant schizophrenia, is linked to metabolic disturbances such as weight gain and metabolic syndrome (MetS). Methods: This systematic review and meta-analysis evaluated the association between HTR2C polymorphisms and these adverse effects. Following PRISMA guidelines, 27 studies (n = 4044 patients, including 1804 clozapine-treated) were analyzed. Results: A meta-analysis revealed that the rs3813929 T allele was associated with a smaller increase in body weight, showing a mean BMI difference of 0.59 kg/m² (95% CI: −1.02 to −0.17; *p* = 0.006), particularly in males. The rs1414334 C allele doubled MetS risk (OR: 2.15; 95% CI: 1.42–3.27; *p* = 0.0003). Haplotype analyses suggested combined genetic effects, though findings for other polymorphisms were inconsistent. Key limitations include study heterogeneity, small sample sizes, and the predominance of mixed antipsychotic regimens (clozapine with other psychotropics) in included studies, potentially confounding metabolic outcomes. Despite this, rs3813929 and rs1414334 emerge as promising pharmacogenetic markers for predicting metabolic risks. Conclusions: These results highlight the need for large-scale, prospective studies across diverse populations to validate associations and optimize personalized monitoring strategies. Implementing genetic screening could enhance early intervention, improving long-term outcomes for clozapine-treated patients. Full article

Antiretroviral therapy (ART) has significantly improved the life expectancy of people living with HIV-1 (PLWH). However, prolonged ART use is linked to metabolic alterations and oxidative stress. The paraoxonase (PON) enzymes, especially PON-1 and PON-2, are critical in maintaining antioxidant balance. Their activity can be influenced by polymorphisms such as Q192R and L55M in PON-1 and A148G and S311C in PON-2. This study examines the impact of these polymorphisms on paraoxonase activity, lipid metabolism, and infection markers in PLWH under various ART regimens. This is a case-control study with 525 participants, 175 healthy controls (HC) and 350 PLWH divided into subgroups: T0 (ART-naïve, n = 48), T1 (ART with reverse transcriptase inhibitors, n = 159), and T2 (ART with protease inhibitors, n = 143). Paraoxonase activity was higher in PLWH (123.0; IQR: 62.0–168.0) compared to HC (91.0; IQR: 48.0–136.0, p < 0.001) but similar between HC and T0 (p = 0.594). T1 (125.0; IQR: 65.5–166.0) and T2 (123.0; IQR: 61.0–182.0) showed higher activity than HC (p = 0.002 and 0.003). Among 61 complete genotypes, 13 were unique to PLWH and 6 to HC (p < 0.001). L55L was more frequent in HC (49.7% vs. 36.9% in PLWH), while M55M was higher in PLWH (p = 0.004). The S311C genotype was more frequent in HC (39.2%) than PLWH (24.9%) (p = 0.003). The L55L genotype conferred 59.9% protection against HIV-1 (OR: 0.401; 95% CI: 0.228–0.704), while the M allele increased susceptibility by ~69% (OR: 1.694; 95% CI: 1.173–2.446). The M55M genotype and/or M allele may be linked to HIV-1 susceptibility. Prolonged ART use elevates PON-1 activity in PLWH. Full article

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on the RET C611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile. Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying the RET C611Y variant in Denmark before 1 April 2021. Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p < 0.001). The mean age at T0N0M0 was 16 years (CI, 12–20), at T1-4N0M0 38 years (CI, 34–42), at TxN1M0 45 years (CI, 38–53) and at TxNxM1 49 years (CI, 36–61). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84). Conclusions: RET C611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population. Full article

Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. Methods: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. Results: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Conclusion: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation. Full article

This study aims to develop low-cost, eco-friendly, and circular economy-compliant composite materials by creating three types of magnetorheological suspensions (MRSs) utilizing lard, carbonyl iron (CI) microparticles, and varying quantities of gelatin particles (GP). These MRSs serve as dielectric materials in cylindrical cells used to fabricate electric capacitors. The equivalent electrical capacitance (C) of these capacitors is measured under different magnetic flux densities ($B\le 160$ mT) superimposed on a medium-frequency electric field (f = 1 kHz) over a period of 120 s. The results indicate that at high values of B, increasing the GP content to 20 vol.% decreases the capacitance C up to about one order of magnitude compared to MRS without GP. From the measured data, the average values of capacitance $C_{\mathrm{m}}$ are derived, enabling the calculation of relative dielectric permittivities (${ϵ}_{\mathrm{r}}^{\prime }$) and the dynamic viscosities ($\eta$) of the MRSs. It is demonstrated that ${ϵ}_{\mathrm{r}}^{\prime }$ and $\eta$ can be adjusted by modifying the MRS composition and fine-tuned through the magnetic flux density B. A theoretical model based on the theory of dipolar approximations is used to show that ${ϵ}_{\mathrm{r}}^{\prime }$, $\eta$, and the magnetodielectric effect can be coarsely adjusted through the composition of MRSs and finely adjusted through the values B of the magnetic flux density. The ability to fine-tune these properties highlights the versatility of these materials, making them suitable for applications in various industries, including electronics, automotive, and aerospace. Full article

Solar-induced chlorophyll fluorescence (SIF) has been widely utilized to track the dynamics of gross primary productivity (GPP). It has been shown that the photochemical reflectance index (PRI), which may be utilized as an indicator of non-photochemical quenching (NPQ), improves SIF-based GPP estimation. However, the influence of weather conditions on GPP estimation using SIF and PRI has not been well explored. In this study, using an open-access dataset, we examined the impact of the clearness index (CI), which is associated with the proportional intensity of solar incident radiation and can represent weather conditions, on soybean GPP estimation using SIF and PRI. The midday PRI (xanthophyll de-epoxidation state) minus the early morning PRI (xanthophyll epoxidation state) yielded the corrected PRI (ΔPRI), which described the amplitude of xanthophyll pigment interconversion during the day. The observed canopy SIF at 760 nm (${\mathrm{S}\mathrm{I}\mathrm{F}}_{\mathrm{T}\mathrm{O}\mathrm{C}\_760}$) was downscaled to the broadband photosystem-level SIF for photosystem II (${\mathrm{S}\mathrm{I}\mathrm{F}}_{\mathrm{T}\mathrm{O}\mathrm{T}\_\mathrm{F}\mathrm{U}\mathrm{L}\mathrm{L}\_\mathrm{P}\mathrm{S}\mathrm{I}\mathrm{I}}$). Our results show that GPP can be accurately estimated using a multi-linear model with ${\mathrm{S}\mathrm{I}\mathrm{F}}_{\mathrm{T}\mathrm{O}\mathrm{T}\_\mathrm{F}\mathrm{U}\mathrm{L}\mathrm{L}\_\mathrm{P}\mathrm{S}\mathrm{I}\mathrm{I}}$ and ΔPRI. The ratio of GPP measured using the eddy covariance (EC) method (${\mathrm{G}\mathrm{P}\mathrm{P}}_{\mathrm{E}\mathrm{C}}$) to GPP estimated using ${\mathrm{S}\mathrm{I}\mathrm{F}}_{\mathrm{T}\mathrm{O}\mathrm{T}\_\mathrm{F}\mathrm{U}\mathrm{L}\mathrm{L}\_\mathrm{P}\mathrm{S}\mathrm{I}\mathrm{I}}$ and ΔPRI exhibited a non-linear correlation with the CI along both the half-hourly (R² = 0.21) and daily scales (R² = 0.25). The GPP estimates using ${\mathrm{S}\mathrm{I}\mathrm{F}}_{\mathrm{T}\mathrm{O}\mathrm{T}\_\mathrm{F}\mathrm{U}\mathrm{L}\mathrm{L}\_\mathrm{P}\mathrm{S}\mathrm{I}\mathrm{I}}$ and ΔPRI were significantly improved by the addition of the CI (for the half-hourly data, R² improved from 0.64 to 0.71 and the RMSE decreased from 8.28 to 7.42 $\mathsf{\mu }$mol•m⁻²•s⁻¹; for the daily data, R² improved from 0.71 to 0.81 and the RMSE decreased from 6.69 to 5.34 $\mathsf{\mu }$mol•m⁻²•s⁻¹). This was confirmed by the validation results. In addition, the GPP estimated using the Random Forest method was also largely improved by considering the influences of the CI. Therefore, our findings demonstrate that GPP can be well estimated using ${\mathrm{S}\mathrm{I}\mathrm{F}}_{\mathrm{T}\mathrm{O}\mathrm{T}\_\mathrm{F}\mathrm{U}\mathrm{L}\mathrm{L}\_\mathrm{P}\mathrm{S}\mathrm{I}\mathrm{I}}$ and ΔPRI, and it can be significantly enhanced by accounting for the CI. These results will be beneficial to vegetation GPP estimation using different remote sensing platforms, especially under various weather conditions. Full article

The purpose of this work was to find a link between the breast cancer (BC)-risk effects of sex hormone-binding globulin (SHBG)-associated polymorphisms and obesity. The study was conducted on a sample of 1498 women (358 BC; 1140 controls) who, depending on the presence/absence of obesity, were divided into two groups: obese (119 BC; 253 controls) and non-obese (239 BC; 887 controls). Genotyping of nine SHBG-associated single nucleotide polymorphisms (SNP)—rs17496332 PRMT6, rs780093 GCKR, rs10454142 PPP1R21, rs3779195 BAIAP2L1, rs440837 ZBTB10, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs8023580 NR2F2, and rs12150660 SHBG—was executed, and the BC-risk impact of these loci was analyzed by logistic regression separately in each group of obese/non-obese women. We found that the BC-risk effect correlated by GWAS with the SHBG-level polymorphism rs10454142 PPP1R21 depends on the presence/absence of obesity. The SHBG-lowering allele C rs10454142 PPP1R21 has a risk value for BC in obese women (allelic model: CvsT, OR = 1.52, 95%CI = 1.10–2.11, and p_perm = 0.013; additive model: CCvsTCvsTT, OR = 1.71, 95%CI = 1.15–2.62, and p_perm = 0.011; dominant model: CC + TCvsTT, OR = 1.95, 95%CI = 1.13–3.37, and p_perm = 0.017) and is not associated with the disease in women without obesity. SNP rs10454142 PPP1R21 and 10 proxy SNPs have adipose-specific regulatory effects (epigenetic modifications of promoters/enhancers, DNA interaction with 51 transcription factors, eQTL/sQTL effects on five genes (PPP1R21, RP11-460M2.1, GTF2A1L, STON1-GTF2A1L, and STON1), etc.), can be “likely cancer driver” SNPs, and are involved in cancer-significant pathways. In conclusion, our study detected an obesity-dependent association of the rs10454142 PPP1R21 with BC in women. Full article