Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Bone Health-Related Nutritional Knowledge and its Association with Calcium-Related Dietary Behaviors and Nutrition Education of Women in their 20s and 30s

Osteoporosis is a major health problem confronting middle-aged women today. Enhancing calcium intake in early adulthood can increase the rate of calcium gain in bone. In this study, we investigated the association of bone health-related nutritional knowledge levels with calcium-related dietary behavior and nutrition education among women. Data were collected using questionnaires from 347 women aged 20∼30 residing in Gyeonggi-do. Subjects were categorized into two groups according to their bone health-related nutritional knowledge (high or low-knowledge group). Knowledge related to bone health and calcium, and dietary habits was assessed, and the preference for and intake frequency of calcium-rich food were collected and analyzed using food frequency questionnaires. The high-knowledge group showed a significantly higher rate of nutritional education experience (33.9%) when compared with the low-knowledge group (18.9%). Not only were the perceptions regarding milk and dairy products more positive in the high-knowledge group (P＜0.05), but the intake frequency of calcium-rich foods, such as tofu, soybean, and anchovies, was also higher in this group compared to the low-knowledge group (P＜0.05). Overall, the preference for all calcium-rich foods was positively correlated to their intake frequency (P＜0.05). Nutrition education experience and the recognition of the need for such education were positively correlated with the bone health-related nutrition knowledge score (P＜0.05). In conclusion, bone health-related nutritional knowledge can affect calcium-related dietary behavior and increase the intake of calcium-rich food of 20∼30-year-old women and this can contribute to the prevention of osteoporosis. To improve bone health-related nutritional knowledge among young women, it may be important to provide nutrition education.

Effect of cinacalcet-mediated parathyroid hormone reduction on vitamin D metabolism in high-fat dietinduced obese mice / 한국영양학회지

Purpose@#Obesity is associated with alterations in vitamin D metabolism and elevation of parathyroid hormone (PTH). Increased PTH level in obesity is likely one of the factors contributing to the dysregulation of vitamin D metabolism. We investigated the effects of lowering the PTH level in high-fat diet-induced obese mice on vitamin D metabolism. @*Methods@#Five-week-old male C57BL/6N mice were fed either with control (10% energy as fat) or high-fat (60% energy as fat) diets ad libitum for 12 weeks, and vehicle or cinacalcet HCl (30 μg/g body weight) was gavaged daily during the final week of the experiment. The following groups were studied: CON (control diet + vehicle), HFD (high-fat diet + vehicle), and HFD-CIN (high-fat diet + cinacalcet HCl). PTH, 1,25-dihydroxyvitamin D (1,25[OH] 2 D), 25-hydroxyvitamin D (25[OH]D), calcium, and phosphate levels in circulation, and the expression of genes related to vitamin D metabolism in the liver and kidneys were determined. @*Results@#Renal 1α-hydroxylase expression in the HFD group was higher than that in the CON group despite the lack of a difference in the PTH levels between the 2 groups. The plasma PTH level in the HFD-CIN group was 60% lower than that in the HFD group (p < 0.05). In parallel, the HFD-CIN group had lower adipose tissue amount (9% lower), renal 1α-hydroxylase expression (48% lower), and plasma 1,25(OH) 2 D concentration (38% lower) than the HFD group. @*Conclusion@#Lowering the PTH levels in high-fat diet-induced obese mice recovered the expression of renal 1α-hydroxylase and might be associated with lower amounts of white adipose tissue.

Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer.However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

The Role of Vitamin D in Adipose Tissue Biology: Adipocyte Differentiation, Energy Metabolism, and Inflammation

Adipose tissue is composed of diverse cell types and plays a major role in energy homeostasis and inflammation at the local and systemic levels. Adipose tissue serves as the main site for vitamin D storage and is among the most important extraskeletal targets of vitamin D which can modulate multiple aspects of adipose tissue biology. Vitamin D may exert inhibitory or stimulatory effects on adipocyte differentiation depending on cell type, stage of differentiation, and the treatment time point. Moreover, vitamin D controls energy metabolism in adipose tissue by affecting fatty acid oxidation, expression of uncoupling proteins, insulin resistance, and adipokine production. Adipose tissue inflammation can have a significant impact on the metabolic disorders often associated with obesity, and vitamin D can modulate the inflammatory response of immune cells and adipocytes within the adipose tissue. This review discusses the role of adipose tissue in vitamin D metabolism, as well as the regulatory role of vitamin D in adipocyte differentiation, adipose tissue energy metabolism, and inflammation, thereby providing insights into the importance of vitamin D in adipose tissue biology.

The Role of Vitamin D in Adipose Tissue Biology: Adipocyte Differentiation, Energy Metabolism, and Inflammation

Adipose tissue is composed of diverse cell types and plays a major role in energy homeostasis and inflammation at the local and systemic levels. Adipose tissue serves as the main site for vitamin D storage and is among the most important extraskeletal targets of vitamin D which can modulate multiple aspects of adipose tissue biology. Vitamin D may exert inhibitory or stimulatory effects on adipocyte differentiation depending on cell type, stage of differentiation, and the treatment time point. Moreover, vitamin D controls energy metabolism in adipose tissue by affecting fatty acid oxidation, expression of uncoupling proteins, insulin resistance, and adipokine production. Adipose tissue inflammation can have a significant impact on the metabolic disorders often associated with obesity, and vitamin D can modulate the inflammatory response of immune cells and adipocytes within the adipose tissue. This review discusses the role of adipose tissue in vitamin D metabolism, as well as the regulatory role of vitamin D in adipocyte differentiation, adipose tissue energy metabolism, and inflammation, thereby providing insights into the importance of vitamin D in adipose tissue biology.

Nutrient modulation of viral infectionimplications for COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has put focus on the importance of a healthy immune system for recovery from infection and effective response to vaccination.Several nutrients have been under attention because their nutritional statuses showed associations with the incidence or severity of COVID-19 or because they affect several aspects of immune function. Nutritional status, immune function, and viral infection are closely interrelated. Undernutrition impairs immune function, which can lead to increased susceptibility to viral infection, while viral infection itself can result in changes in nutritional status. Here, we review the roles of vitamins A, C, D, and E, and zinc, iron, and selenium in immune function and viral infection and their relevance to COVID-19.

Effects of in vitro vitamin D treatment on function of T cells and autophagy mechanisms in high-fat diet-induced obese mice

BACKGROUND/OBJECTIVES@#Obesity is associated with the impaired regulation of T cells characterized by increased numbers of Th1 and Th17 cells and the dysregulation of vitamin D metabolism. Both obesity and vitamin D have been reported to affect autophagy; however, a limited number of studies have investigated the effects of vitamin D on T cell autophagy in obese mice. Therefore, we aimed to determine whether in vitro treatment with vitamin D affects the proliferation, function, and autophagy of T cells from obese and control mice.MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed control or high-fat diets (10% or 45% kcal fat: CON or HFDs, respectively) for 12 weeks. Purified T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies and cultured with either 10 nM 1,25(OH)2D3 or 0.1% ethanol (vehicle control). The proliferative response; expression of CD25, Foxp3, RORγt, and autophagy-related proteins (LC3A/B, SQSTM1/P62, BECLIN-1, ATG12); and the production of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and IL-10 by T cells were measured. @*RESULTS@#Compared with the CON group, T cell proliferation tended to be lower, and the production of IFN-γ was higher in the HFD group. IL-17A production was reduced by 1,25(OH)2D3 treatment in both groups. The LC3 II/I ratio was higher in the HFD group than the CON group, but P62 did not differ. We observed no effect of vitamin D treatment on T cell autophagy. @*CONCLUSIONS@#Our findings suggest that diet-induced obesity may impair the function and inhibit autophagy of T cells, possibly leading to the dysregulation of T cell homeostasis, which may be behind the aggravation of inflammation commonly observed in obesity.

Selonsertib Inhibits Liver Fibrosis via Downregulation of ASK1/ MAPK Pathway of Hepatic Stellate Cells

Liver fibrosis constitutes a significant health problem worldwide due to its rapidly increasing prevalence and the absence of specific and effective treatments. Growing evidence suggests that apoptosis-signal regulating kinase 1 (ASK1) is activated in oxidative stress, which causes hepatic inflammation and apoptosis, leading to liver fibrogenesis through a mitogen-activated protein kinase (MAPK) downstream signals. In this study, we investigated whether selonsertib, a selective inhibitor of ASK1, shows therapeutic efficacy for liver fibrosis, and elucidated its mechanism of action in vivo and in vitro. As a result, selonsertib strongly suppressed the growth and proliferation of hepatic stellate cells (HSCs) and induced apoptosis by increasing Annexin V and TUNEL-positive cells. We also observed that selonsertib inhibited the ASK1/MAPK pathway, including p38 and c-Jun N-terminal kinase (JNK) in HSCs. Interestingly, dimethylnitrosamine (DMN)-induced liver fibrosis was significantly alleviated by selonsertib treatment in rats. Furthermore, selonsertib reduced collagen deposition and the expression of extracellular components such as α-smooth muscle actin (α-SMA), fibronectin, and collagen type I in vitro and in vivo. Taken together, selonsertib suppressed fibrotic response such as HSC proliferation and extracellular matrix components by blocking the ASK1/MAPK pathway. Therefore, we suggest that selonsertib may be an effective therapeutic drug for ameliorating liver fibrosis.

Multimodal Diagnostic Approach for Synovitis of the Wrist / 대한정형외과학회잡지

PURPOSE: The purpose of this study was to suggest a multimodal diagnostic approach to determine the cause of the disease in patients diagnosed with synovitis of the wrist and who underwent synovectomy. MATERIALS AND METHODS: Twenty-nine patients, who underwent contrast magnetic resonance imaging (MRI) preoperatively and synovectomy from January 2000 to December 2013, were reviewed retrospectively. Among them, 17 patients underwent a Tc99m white blood cell (WBC) scan preoperatively. In patients who met the diagnostic criteria of rheumatoid arthritis (RA), the diagnosis was confirmed as RA if the MRI finding or histology was compatible with RA. If the MRI finding and histology were disparate, the final diagnosis was made based on the histologic finding. RESULTS: Of the nine patients who met the diagnostic criteria of RA, seven patients were finally diagnosed as RA and two patients as tuberculous arthritis. Of the 20 patients who did not meet the diagnostic criteria of RA, the MRI findings and histology were consistent with the same disease in 12 patients. In the remaining eight patients, five were diagnosed with nonspecific chronic synovitis, one with RA, and two with tuberculous arthritis based on the clinical findings, MRI, and histology findings. CONCLUSION: MRI and a WBC scan are very useful imaging modalities for diagnosing the causative condition of the wrist synovitis. A histology evaluation after synovectomy can also be useful in cases with a difficult diagnosis or are refractory to medications.

Effect of preoperative pregabalin on postoperative pain after gastrectomy / 영남의대학술지

BACKGROUND: Pregabalin has been studied as a single or multimodal analgesic drug for postoperative pain management in different types of surgeries. We evaluated the analgesic effect of 150 mg of pregabalin in resolving post-gastrectomy pain.METHODS: Forty-four patients were randomized into two groups: a pregabalin group that received oral pregabalin (150 mg) 2 h before anesthetic induction, and a control group that received placebo tablets at the same time. Data on postoperative pain intensity (visual analog scale [VAS], at 30 min, 2 h, 4 h, and 24 h), consumption of fentanyl in patient-controlled analgesia (PCA), and the proportion of patients requiring rescue analgesics at different time intervals (0–2 h, 2–4 h, and 4–24 h) were collected during the 24 h postoperative period.RESULTS: The VAS scores did not show significant differences at any time point and consumption of fentanyl in PCA and the proportion of patients requiring rescue analgesics did not differ between the two groups. The groups did not differ in the occurrence of dizziness, sedation, and dry mouth.CONCLUSION: A preoperative 150 mg dose of pregabalin exerts no effect on acute pain after gastrectomy.

Effect of preoperative pregabalin on postoperative pain after gastrectomy / 영남의대학술지

BACKGROUND@#Pregabalin has been studied as a single or multimodal analgesic drug for postoperative pain management in different types of surgeries. We evaluated the analgesic effect of 150 mg of pregabalin in resolving post-gastrectomy pain.@*METHODS@#Forty-four patients were randomized into two groups: a pregabalin group that received oral pregabalin (150 mg) 2 h before anesthetic induction, and a control group that received placebo tablets at the same time. Data on postoperative pain intensity (visual analog scale [VAS], at 30 min, 2 h, 4 h, and 24 h), consumption of fentanyl in patient-controlled analgesia (PCA), and the proportion of patients requiring rescue analgesics at different time intervals (0–2 h, 2–4 h, and 4–24 h) were collected during the 24 h postoperative period.@*RESULTS@#The VAS scores did not show significant differences at any time point and consumption of fentanyl in PCA and the proportion of patients requiring rescue analgesics did not differ between the two groups. The groups did not differ in the occurrence of dizziness, sedation, and dry mouth.@*CONCLUSION@#A preoperative 150 mg dose of pregabalin exerts no effect on acute pain after gastrectomy.

Factors Affecting Length of Hospital Stay and Mortality in Infected Diabetic Foot Ulcers Undergoing Surgical Drainage without Major Amputation

This study aimed to investigate factors affecting length of hospital stay and mortality of a specific group of patients with infected diabetic foot ulcer who underwent surgical drainage without major amputation, which is frequently encountered by orthopedic surgeons. Data on length of hospital stay, mortality, demographics, and other medical information were collected for 79 consecutive patients (60 men, 19 women; mean age, 66.1 [SD, 12.3] yr) with infected diabetic foot ulcer who underwent surgical drainage while retaining the heel between October 2003 and May 2013. Multiple linear regression analysis was performed to determine factors affecting length of hospital stay, while multiple Cox regression analysis was conducted to assess factors contributing to mortality. Erythrocyte sedimentation rate (ESR, P=0.034), glycated hemoglobin (HbA1c) level (P=0.021), body mass index (BMI, P=0.001), and major vascular disease (cerebrovascular accident or coronary artery disease, P=0.004) were significant factors affecting length of hospital stay, whereas age (P=0.005) and serum blood urea nitrogen (BUN) level (P=0.024) were significant factors contributing to mortality. In conclusion, as prognostic factors, the length of hospital stay was affected by the severity of inflammation, the recent control of blood glucose level, BMI, and major vascular disease, whereas patient mortality was affected by age and renal function in patients with infected diabetic foot ulcer undergoing surgical drainage and antibiotic treatment.

Diet-Related Behaviors and Food Preference of Indonesian / 대한지역사회영양학회지

As Korea is moving toward multicultural society, the number of Muslim, whose religion has a great influence on diet-related behaviors, is increasing in Korea. Since the number of immigrants from Indonesia ranks within top ten in Korea and Indonesia is one of the most representative Islamic countries in Asia, understanding the diet-related behaviors and food preferences of Indonesians is needed. This study was conducted to investigate diet-related behaviors, factors affecting the diet-related perceptions, and food preferences of the Indonesians. The subjects included 500 Indonesians dwelling in Jakarta, Indonesia. About ninety % of the subjects in this study were Muslims. They did not eat pork and dog meat for religious reason and they practiced fasting during Ramadan period. Indonesians avoided pineapple, durian, and hot foods during pregnancy and usually ate vegetables and fruits after birth, which seemed to be due to sociocultural influence. Among the subjects, 21.5% were obese and major health problems reported were hypertension and hyperlipidemia. Their preference for fried food items might have contributed to health problems. Subjects had meals mostly at home (2.3 times/day) and dined out occasionally (1.2 times/ week) at Indonesian restaurants (56.6%) or family restaurants (21.0%). In conclusion, Indonesians had home-based and native food-oriented dietary life with strong religious and sociocultural influence on food choices. Further research on specific nutrient intake analysis is needed to better understand and to improve dietary life of Indonesians in Korea.

Innominate Artery Rupture after Blunt Chest Trauma / 대한흉부외과학회지

A rupture of an innominate artery caused by blunt trauma is relatively rare because this artery is short and protected by the chest bony cage. This report describes a 25-year-old man who suffered a traffic accident, that resulted in an innominate artery rupture, which was detected by a chest computed tomogram and angiogram. This patient underwent urgent surgery through a right clavicular incision and median sternotomy without a cardiopulmonary bypass due to multiple injuries. An approximately 3 cm sized injury was found from the innominate artery to the proximal right subclavian artery and the origin of the common carotid artery. The injured lesion was repaired with a saphenous vein patch. After surgery, he was discharged from hospital without complications.

Temperament and Charcater Dimensions of Posttraumatic Stress Disorder in Burn Patients

OBJECTIVE: The aim of this study was to evaluate the temperament and character profiles of the patients with posttraumatic stress disorder(PTSD) after burn injury. METHODS: The study subjects consisted of 23 PTSD patients after burn injury, 24 patients not being diagnosed as PTSD after burn injury(non-PTSD) and 53 healthy controls. The assessment of PTSD was performed using clinician administered PTSD scale. All participants were instructed to complete the Temperament and Character Inventory(TCI), the Beck Depression Inventory and the State and Trait Anxiety Inventory of Spielberger. RESULTS: The PTSD group after burn injury, compared with the non-PTSD group and the normal controls, had the higher novelty seeking and harm avoidance scores. But there were no differences in other dimensions in the TCI among the three groups. CONCLUSION: The results of this study suggest that the PTSD group after burn injury showed the specific properties of temperament and character compared with the non-PTSD group and the normal group.

Primary Trabeculectomy with Mitomycin C for Medically Uncontrolled Angle Closure Glaucoma

PURPOSE: To report the results of primary trabeculectomy with mitomycinmitomycin C (MMC) for medically uncontrolled, primary angle-closure glaucoma. METHODS: A retrospective study of 20 eyes from 18 consecutive patients with medically uncontrolled primary angle-closure glaucoma who underwent trabeculectomy with MMC, from 1997 to 2000. RESULTS: The mean follow up was 33.9 +/- 12.9 months (range 24~60). After trabeculectomy with MMC, IOP remained below 22 mmHg in 17 eyes (85%) with or without medication. Postoperative complications occurred in 5 eyes (25%). CONCLUSIONS: Trabeculectomy with MMC resulted in favorable long-term IOP control and relatively low complications in medically unresponsive acute angle-closure glaucoma.

Mucoepidermoid Carcinoma of the Lung: A case report / 대한흉부외과학회지

Mucoepidermoid carcinoma of the lung is extremely rare. This rare tumor arise beyond the carina, usually main stem bronchi, but occasionally in lobar or segmental airways. This tumor presents with symptoms of bronchial irritation or obstruction. Distant metastasis is an uncommon, therefore complete surgical resection is the treatment of the choice. The prognosis of this tumor correlates with the histologic grade of the tumor. We experienced a case of mucoepidermoid carcinoma arising from the right middle lobe, which was treated with the right middle lobectomy, with good result. We report this case and follow-up of the patient.

Lack of association between rheumatoid arthritis and vitamin D receptor polymorphisms in Koreans / 대한내과학회지

BACKGROUND: The purpose of this study was to determine whether the distribution of vitamin D receptor (VDR) polymorphisms in rheumatoid arthritis (RA) patients group is different from that of the control group and whether there is a relationship between VDR genotype and radiographic severity or bone mineral density (BMD) of RA patients. METHODS: The VDR genotype was determined by polymerase chain reaction and digestion with three restriction enzymes Taq I, Apa I and Bsm I in 78 healthy women and 97 female RA patients. Hand X-rays were scored by Larsen's method and bone mineral density was measured by dual energy X-ray absorptiometry (DEXA) in RA patients. RESULTS: VDR genotypic distributions in Koreans were much different from Caucasians in each control and RA patient groups. Especially, "tt" allele and "BB" allele were very rare, prominently differentiating from Caucasians. But within Koreans, no significant difference of VDR genotypic frequency was observed between control group and RA patients group. And there was no significant relationship of VDR genotype with radiographic scores, nor with BMD scores in RA patients. CONCLUSION: The distribution of VDR polymorphisms in Korean RA patients was not different from controls. The VDR polymorphisms correlate neither with the radiographic severity of RA, nor with BMD scores in Korean RA patients.

Lack of Association Between Osteoarthritis of the Knee and Gene Polymorphisms of VDR in Korean Postmenopausal Women / 대한류마티스학회지

OBJECTIVE: To determine whether polymorphisms of the Vitamin D receptor (VDR)gene,known to be associated with osteoporosis and/or osteoarthritis (OA) in Caucasians,might also relate to the risk of OA and osteoporosis in Korean postmenopausal women METHODS: A population of 130 postmenopausal women,including 76 healthy controls and 54 knee OA patients,were studied using anteroposterior radiographs of the knee,which were graded for OA according to the Kellgren classification system.The VDR genotype was determined by using polymerase chain reaction and by digestion with the three restriction enzymes Taq I,Bsm I,and Apa I.Femoral neck bone mineral density (BMD)was assessed in all participants by dual energy X-ray absorptiometry . RESULTS: VDR genotype frequency distributions in Koreans were much different from Caucasian's both in the OA group and the control group.Especially, "t t", "B B" and "A A" genotype were very rare,prominently differentiating from Caucasians.But within Koreans,no significant differences in VDR genotype frequencies were observed between OA cases and controls.VDR genotype was not significantly associated with the radiographic grades of OA.And there were no significant relationships of VDR genotype with BMD scores in each group. CONCLUSION: In Korean postmenoposal women,the VDR gene polymorphisms do not significantly contribute to an increased prevalence of knee OA or to differences in BMD.VDR genotype analysis would not be helpful for assessing the risk of knee OA in Koreans because :(1)there is no correlation of VDR genotypes with the radiographic severity of OA ;and (2)there is a more skewed distribution of VDR genotypes in Korean population compared to the Caucasian's .