Donor body mass index over 30 is no barrier for pure laparoscopic donor right hepatectomy.

Backgrounds/Aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30. Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed. Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar. Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.

Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes.

ABSTRACT: Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes, with a limit of detection of 0.2%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In conclusion, mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression and may help upfront TKI selection.

Text Extraction and Standardization System Development for Pathological Records in the Korea Biobank Network.

In Korea, the Korea Centers for Disease Control and Prevention operates the Korea BioBank Network (KBN). KBN has pathological records that collected in Korea and it is useful dataset for research. In this study, we established system that time efficient and reduced error by step-by-step data extraction process from KBN pathological records. We tested the extraction process by 769 lung cancer cohorts and 1292 breast cancer cohorts and accuracy is 91%. We expect this system can be used to efficiently process data from multiple institutions, including Korea BioBank Network.

Pure laparoscopic donor hepatectomy: Experience of 556 cases at Seoul National University Hospital.

Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.

Evaluation of the efficacy and safety of conversion from the tacrolimus capsule to tablet in stable liver transplant recipients with maintenance therapy: a 24-week, open-label, single-center, phase IV exploratory clinical study.

Purpose: The tablet form of tacrolimus is more convenient for drug ingestion than the capsule form. We examined the efficacy and safety of tacrolimus tablets and a satisfaction survey after formula conversion in liver transplant (LT) recipients. Methods: This study was an open-label, prospective clinical trial for tacrolimus formula 1:1 conversion from capsule to tablet in 41 adult LT recipients with tacrolimus maintenance therapy of more than 1 month. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) within 24 weeks. Surveys 1 week before and 4 weeks after formula conversion were conducted for total daily dose of medication, number, scale of discomfort and satisfaction. Results: The overall incidence of BPAR was 0% and there was no graft loss or patient death. The incidence of adverse effects was 34.1% (n = 14) after formula conversion. The most common severe adverse effect was abnormal liver function test (n = 5): biliary complications (n = 4) and alcoholic recidivism (n = 1). Total daily dose and number of tacrolimus doses were significantly lower after formula conversion (P < 0.05) without changes in trough level. According to survey analysis, there was no significant difference in discomfort and satisfaction scales from capsule to tablet conversion (P < 0.05). Conclusion: The present study suggests that the new tablet formula can be a useful treatment option to maintain a consistent level of tacrolimus with a lower total daily dose and number in adult LT recipients.

Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a low-risk thyroid tumor with a favorable prognosis. Nonetheless, differentiating NIFTP from other thyroid tumors remains challenging, necessitating reliable diagnostic markers. This study is aimed at discovering NIFTP-specific mRNA markers through RNA sequencing analysis of thyroid tumor tissues. We performed mRNA expression profiling for 74 fresh frozen thyroid tissue samples, including NIFTP and benign and malignant follicular-cell-derived tumors. NIFTP/malignant tumors showed 255 downregulated genes and 737 upregulated genes compared to benign tumors. Venn diagram analysis revealed 19 significantly upregulated and 7 downregulated mRNAs in NIFTP. Akaike information criterion analysis allowed us to select OCLN, ZNF423, LYG1, and AQP5 mRNA markers. We subsequently developed a predictive model based on logistic regression analysis using these four mRNAs, which we validated in independent samples (n = 90) using a qRT-PCR assay. This model demonstrated high accuracy in predicting NIFTP in discovery dataset (AUC (area under the receiver operating characteristic) = 0.960) and the validation dataset (AUC = 0.757). Our results suggest that OCLN, ZNF423, LYG1, and AQP5 mRNA markers might serve as reliable molecular markers for identifying NIFTP among other thyroid tumors, ultimately aiding in accurate diagnosis and management of NIFTP patients.

Recurrence in patients with totally necrotic nodules of hepatocellular carcinoma after liver transplantation: "totally" an inaccurate description.

Purpose: Total necrosis of hepatocellular carcinoma (HCC) achieved via locoregional treatment (LRT) is considered to indicate a lack of tumor viability. Nonetheless, there is insufficient evidence of recurrence after liver transplantation (LT) in patients with such a status. The aim of this study was to investigate the prognosis of patients diagnosed with totally necrotic nodules upon explant hepatectomy after LT. Methods: We conducted a retrospective study of patients diagnosed with totally necrotic nodules after LT for HCC. A total of 165 patients with HCC who underwent living- or deceased-donor LT from 2000 to 2020 in our hospital were included. Results: A total of 5 patients (3.0%) exhibited HCC recurrence during a median follow-up of 84 months (range, 4-243 months) after LT. The 5-year overall and recurrence-free survival rates of these patients were 92.8% and 92.2%, respectively. Four patients in the HCC-recurrence group (80.0%) died even after further treatment, including transarterial chemoembolization, surgery, and systemic treatment. Both univariate and multivariate analyses of clinicopathological factors identified a maximum diameter of the totally necrotic nodules of >5 cm as the only factor associated with tumor recurrence following LT (P = 0.005 and P = 0.009, respectively). Conclusion: Total necrosis of HCC via LRT yielded excellent survival outcomes for patients undergoing LT. Nevertheless, patients with large tumors should be considered at high risk of recurrence after LT, suggesting the need for their active surveillance during the follow-up period.

Text Extraction and Standardization System Development for Pathological Records in the Korea Biobank Network.

In Korea, the Korea Centers for Disease Control and Prevention operates the Korea BioBank Network (KBN). KBN has pathological records that collected in Korea and it is useful dataset for research. In this study, we established system that time efficient and reduced error by step-by-step data extraction process from KBN pathological records. We tested the extraction process by 769 lung cancer cohorts and 1292 breast cancer cohorts and accuracy is 91%. We expect this system can be used to efficiently process data from multiple institutions, including Korea BioBank Network.

Posttransplant sequential adrenal and spine metastasis of hepatocellular carcinoma responsive to combined regorafenib and radiotherapy: a case report.

Adrenal and spinal metastases of hepatocellular carcinoma (HCC) are rare entities with significant morbidity and mortality, particularly after liver transplantation (LT). We report a case of a 49-year-old man who underwent LT for hepatitis B-related end-stage liver disease and HCC (single 4.5 cm lesion [T1N0], without vascular invasion) in 2016. Eighteen months later, adrenal metastasis and hepatitis B seropositive conversion were developed with normal serum tumor. Adrenal metastasis was treated with radiation therapy (RT) and hepatitis B showed spontaneous seronegative conversion. However, 35 months later, spinal metastasis occurred with elevation of the protein induced by vitamin K absence or antagonist-II (PIVKA-II) level (197 mAU/mL), along with hepatitis B seropositive conversion. After sorafenib, sequential regorafenib with RT led to partial response of the spinal lesions, along with hepatitis B seronegative conversion and normal PIVKA-II levels. After 9 months of regorafenib combined with RT, two recurrent lesions were found, as well as hepatitis B seropositive conversion and lesions were treated with transarterial chemoembolization. The patient survived for more than 71 months after LT and 53 months after recurrence under various combinations of therapy. Combined systemic and locoregional therapies can be a treatment option for HCC recurrence, even in LT patients.

Generation and analysis of whole-genome sequencing data in human mammary epithelial cells.

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis.

Portal vein reconstruction in pediatric liver transplantation using end-to-side jump graft: A case report.

Attenuated portal vein (PV) flow is challenging in pediatric liver transplantation (LT) because it is unsuitable for classic end-to-end jump graft reconstruction from a small superior mesenteric vein (SMV). We thus introduce a novel technique of an end-to-side jump graft from SMV during pediatric LT using an adult partial liver graft. We successfully performed two cases of end-to-side retropancreatic jump graft using an iliac vein graft for PV reconstruction. One patient was a 2-year-old boy with hepatoblastoma and a Yerdel grade 3 PV thrombosis who underwent split LT. Another patient was an 8-month-old girl who had biliary atresia and PV hypoplasia with stenosis on the confluence level of the SMV; she underwent retransplantation because of graft failure related to PV thrombosis. After native PV was resected at the SMV confluence level, an end-to-side reconstruction was done from the proximal SMV to an interposition iliac vein. The interposition vein graft through posterior to the pancreas was obliquely anastomosed to the graft PV. There was no PV related complication during the follow-up period. Using a jump vascular graft in an end-to-side manner to connect the small native SMV and the large graft PV is a feasible treatment option in pediatric recipients with inadequate portal flow due to thrombosis or hypoplasia of the PV.

Chemical Constituents of the Flowers of Pueraria lobata and Their Cytotoxic Properties.

The flower of Pueraria lobata (Puerariae Flos) is a reddish-purple to violet-purple flower that blooms between July and September. In our preliminary study, Puerariae Flos extract exhibited significant activity against a human ovarian cancer cell line. This research aims to identify the active compounds in Pueraria Flos. By repeated chromatography, one new tryptophan derivative (1), two new flavanones (4 and 5), and 19 known compounds, including tryptophan derivatives (2 and 3), flavonoids (6-9), isoflavonoids (10-20), a flavonolignan (21), and a phenolic compound (22), were isolated from a methanol extract of Puerariae Flos. The structures of new compounds were elucidated as 13-N-benzoyl-l-tryptophan-1-N-ß-d-glucopyranoside (1), 2-hydroxy-5-methoxy-naringenin (4), and 2-hydroxy-5-methoxy-naringenin 7-O-ß-d-glucopyranoside (5). Among the isolates, afromosin (17), tectorigenin (11), apigenin (8), glycitein (16), (-)-hydnocarpin (21), irilin D (12), irisolidone 7-O-glucoside (14), and genistein (10) showed cytotoxicity against human ovarian cancer cell line A2780. Apigenin (8) and (-)-hydnocarpin (21) were the most active (IC50 values of 9.99 and 7.36 µM, respectively).

Anti-Hair Loss Effect of Adenosine Is Exerted by cAMP Mediated Wnt/ß-Catenin Pathway Stimulation via Modulation of Gsk3ß Activity in Cultured Human Dermal Papilla Cells.

In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/ß-catenin pathway by modulating the activity of Gsk3ß in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3ß was increased. Furthermore, the expression of ß-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/ß-catenin signaling through the activation of the adenosine receptor and Gsk3ß plays a critical role in transmitting the signals from the adenosine receptor to ß-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.

Comparative genomics and selection analysis of Yeonsan Ogye black chicken with whole-genome sequencing.

Yeonsan Ogye (OGYE; Gallus gallus domesticus) is a rare indigenous chicken breed that inhabits the Korean Peninsula. This breed has completely black coloring, including plumage, skin, eyes, beak, and internal organs. Despite these unique morphological characteristics, the population of OGYE has declined without in-depth research into their genome research. Therefore, this study aimed to compare the whole genome of OGYE to 12 other chicken populations, including ancestral breed, commercial breeds, Chinese indigenous breeds, and Korean native chickens. We focused on revealing the selection signature of OGYE, which has occurred through environmental pressures in the Korean Peninsula. Genome-wide selection analysis has identified local adaptation traits, such as egg development, that contribute to fetal viability and innate immune response to prevent viral and microbes infection in OGYE. In particular, SPP1 (Secreted Phosphoprotein 1), HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1), and P2RX4 (Purinergic Receptor P2X 4) could have considerable involvement in egg development and RNASEL (Ribonuclease L), BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1), and TLR4 (Toll-Like Receptor 4) are crucial for the determination of the innate immune response. This study revealed the unique genetic diversity of OGYE at the genome-wide level. Furthermore, we emphasized the sustainable management of genetic resources and formulated breeding strategies for livestock on the Korean Peninsula.

Antiandrogenic activity of Riboflavin 5'-phosphate (FMN) in 22Rv1 and LNCaP human prostate cancer cell lines.

The androgen receptor is a hormone activated transcription factor that regulates the development and maintenance of male characteristics and represents one of the most well-established drug targets, being implicated not only in prostate cancer but also in many non-cancerous human diseases including androgenetic alopecia, acne vulgaris, and hirsutism. In this study, the antiandrogenic effects of FMN were investigated in 22Rv1 and LNCaP prostate cancer cells. FMN inhibited dihydrotestosterone (DHT)-induced protein expression of androgen receptor in 22Rv1cells. In another prostate cancer LNCaP cells, FMN decreased the protein level of DHT-induced prostate specific antigen (PSA). In addition, FMN downregulated DHT-induced mRNA expression of androgen regulated genes in both cell lines, showing less prominent inhibition in 22Rv1cells where androgen receptor had been significantly decreased by FMN. FMN was found to bind androgen receptor, demonstrating that it acted as a competitive androgen receptor antagonist. FMN increased the phosphorylation of Akt in 22Rv1 cells and this increment was abrogated by PI3K inhibitor wortmannin, resulting in a rescued androgen receptor protein level which was decreased by FMN. Additionally, FMN was found to increase the mRNA and protein level of E3 ligase mouse double minute 2. Our data suggest that the androgen receptor signaling is regulated through PI3K-Akt-MDM2 pathway in 22Rv1 cells. Together, our results indicate that FMN facilitated the degradation of androgen receptor in 22Rv1 cells and inhibited the expression of androgen regulated genes by competing the binding of DHT to androgen receptor in LNCaP cells, demonstrating its therapeutic potential as an antiandrogen.

Production of active Exendin-4 in Nicotiana benthamiana and its application in treatment of type-2 diabetics.

GLP-1 (Glucagon-like peptide-1) is a peptide that stimulates insulin secretion from the ß-cell for glycemic control of the plasma blood glucose level. Its mimetic exenatide (synthetic Exendin-4) with a longer half-life of approximately 3.3-4 h is widely used in clinical application to treat diabetes. Currently, exenatide is chemically synthesized. In this study, we report that the GLP-1 analogue recombinant Exendin-4 (Exdn-4) can be produced at a high level in Nicotiana benthamiana, with an estimated yield of 50.0 µg/g fresh biomass. For high-level expression, we generated a recombinant gene, B:GB1:ddCBD1m:8xHis : Exendin-4 (BGC : Exdn-4), for the production of Exendin-4 using various domains such as the BiP signal peptide, the GB1 domain (B1 domain of streptococcal G protein), a double cellulose binding domain 1 (CBD1), and 8 His residues (8xHis) to the N-terminus of Exendin-4. GB1 was used to increase the expression, whereas double CBD1 and 8xHis were included as affinity tags for easy purification using MCC beads and Ni2+-NTA resin, respectively. BGC : Exdn-4 was purified by single-step purification to near homogeneity using both Ni2+-NTA resin and microcrystalline cellulose (MCC) beads. Moreover, Exdn-4 without any extra residues was produced from BGC : Exdn-4 bound onto MCC beads by treating with enterokinase. Plant-produced Exdn-4 (Exendin-4) was as effective as chemically synthesized Exendin-4 in glucose-induced insulin secretion (GIIS) from mouse MIN6m9 cells a pancreatic beta cell line.

Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/ß-Catenin Pathway Stimulation by Regulating GSK3b Activity.

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/ß-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFß) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/ß-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.

Quercitrin Stimulates Hair Growth with Enhanced Expression of Growth Factors via Activation of MAPK/CREB Signaling Pathway.

The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors-such as bFGF, KGF, PDGF-AA, and VEGF-were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway.

Genetically, Dietary Sodium Intake Is Causally Associated with Salt-Sensitive Hypertension Risk in a Community-Based Cohort Study: a Mendelian Randomization Approach.

PURPOSE OF REVIEW: Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR). RECENT FINDINGS: We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR, 0.356; 95% CI, 0.236-0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR, 2.114; 95% CI, 2.004-2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1 mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype. Our findings suggest that dietary sodium intake may be causally associated with hypertension risk.