Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries.

Ovarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains unclear how to overcome poor follicular development with aging. Upregulation of the low-density lipoprotein receptor (LDLR) enhances oogenesis and follicular development in mouse ovaries. This study investigated whether upregulation of LDLR expression using lovastatin enhances ovarian activity in mice. We performed superovulation using a hormone and used lovastatin to upregulate LDLR. We histologically analyzed the functional activity of lovastatin-treated ovaries and investigated gene and protein expression of follicular development markers, using RT-qPCR and Western blotting. Histological analysis showed that lovastatin significantly increased the numbers of antral follicles and ovulated oocytes per ovary. The in vitro maturation rate was 10% higher for lovastatin-treated ovaries than for control ovaries. Relative LDLR expression was 40% higher in lovastatin-treated ovaries than in control ovaries. Lovastatin significantly increased steroidogenesis in ovaries and promoted the expression of follicular development marker genes such as anti-Mullerian hormone, Oct3/4, Nanog, and Sox2. In conclusion, lovastatin enhanced ovarian activity throughout follicular development. Therefore, we suggest that upregulation of LDLR may help to improve follicular development in clinical settings. Modulation of lipoprotein metabolism can be used with assisted reproductive technologies to overcome ovarian aging.

Relationship between low skeletal muscle mass, sarcopenic obesity and left ventricular diastolic dysfunction in Korean adults.

BACKGROUND: Heart failure with preserved ejection fraction is an emerging global health issue attributed to an ageing population. However, the association between low skeletal muscle mass, sarcopenic obesity, and left ventricular diastolic dysfunction remains unclear. In the current study, we aimed to investigate the relationship between low skeletal muscle mass, sarcopenic obesity, and diastolic dysfunction in a large cohort of Korean adults. METHODS: We conducted a cross-sectional study of 31 258 subjects who underwent health examinations at Samsung Medical Centre's Health Promotion Centre in Seoul, Republic of Korea. Relative skeletal muscle mass was calculated using the skeletal muscle mass index [SMI (%) = appendicular skeletal muscle mass (kg)/body weight (kg) × 100], which was estimated by bioelectrical impedance analysis. Cardiac structure and function were evaluated by echocardiography. RESULTS: Amongst the 31 258 subjects, 3058 (9.78%) were determined to have diastolic dysfunction. The odds ratio (OR) of diastolic dysfunction was 1.56 [95% confidence interval (CI): 1.31-1.85; p for trend <0.001] for the lowest SMI tertile relative to the highest SMI tertile following multivariable adjustment. Furthermore, the risk of diastolic dysfunction was much higher in the sarcopenic obesity (OR: 1.70, 95% CI: 1.44-1.99), followed by in the obesity-only (OR: 1.40, 95% CI: 1.21-1.62), and sarcopenia-only (OR: 1.32, 95% CI: 1.08-1.61) when compared with the nonobese, nonsarcopenic group. These results remained consistent amongst the elderly (age ≥ 65 years). CONCLUSIONS: Our findings demonstrate that lower skeletal muscle mass and sarcopenic obesity are strongly associated with diastolic dysfunction in middle-aged and older adults.

Validation of the effectiveness of a digital integrated healthcare platform utilizing an AI-based dietary management solution and a real-time continuous glucose monitoring system for diabetes management: a randomized controlled trial.

BACKGROUND: Despite the numerous healthcare smartphone applications for self-management of diabetes, patients often fail to use these applications consistently due to various limitations, including difficulty in inputting dietary information by text search and inconvenient and non-persistent self-glucose measurement by home glucometer. We plan to apply a digital integrated healthcare platform using an artificial intelligence (AI)-based dietary management solution and a continuous glucose monitoring system (CGMS) to overcome those limitations. Furthermore, medical staff will be performing monitoring and intervention to encourage continuous use of the program. The aim of this trial is to examine the efficacy of the program in patients with type 2 diabetes mellitus (T2DM) who have HbA1c 53-69 mmol/mol (7.0-8.5%) and body mass index (BMI) ≥ 23 mg/m2. METHODS: This is a 48-week, open-label, randomized, multicenter trial consisting of patients with type 2 diabetes. The patients will be randomly assigned to three groups: control group A will receive routine diabetes care; experimental group B will use the digital integrated healthcare platform by themselves without feedback; and experimental group C will use the digital integrated healthcare platform with continuous glucose monitoring and feedback from medical staff. There are five follow-up measures: baseline and post-intervention at weeks 12, 24, 36, and 48. The primary end point is change in HbA1c from baseline to six months after the intervention. DISCUSSION: This trial will verify the effectiveness of a digital integrated healthcare platform with an AI-driven dietary solution and a real-time CGMS in patients with T2DM. TRIAL REGISTRATION: Clinicaltrials.gov NCT04161170, registered on 08 November 2019. https://clinicaltrials.gov/ct2/show/NCT04161170?term=NCT04161170&draw=2&rank=1.

Clinical factors associated with the recovery of cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in diabetes patients. Although several risk factors for CAN progression have been established, whether CAN is reversible remains unclear and the clinical factors associated with CAN recovery have not been identified. This study aimed to determine clinical factors related to CAN recovery. METHODS: Type 2 diabetes patients with CAN but free of cardiovascular disease at baseline were enrolled and followed for 2-3 years in this retrospective longitudinal study. CAN was classified as early (one abnormal parasympathetic test), definite (two or more abnormal parasympathetic tests), severe (definite plus orthostatic hypotension), or atypical (early plus orthostatic hypotension or orthostatic hypotension alone) based on Ewing's method. CAN recovery was classified as partial or complete: Partial recovery was defined as one-step improvement in CAN stage (early to normal, definite to early, or severe to definite), including the disappearance of only one abnormal result in any stage. Complete recovery was defined as normalization from definite or severe CAN. RESULTS: Among 759 subjects with CAN, 29.9% (n = 227) experienced CAN recovery, and 1.2% (n = 9) recovered completely. In a multivariate model, younger age (odds ratio [OR] per 5-year decrease 1.49; 95% confidence interval [CI] 1.25-1.78, P < 0.001), shorter duration of diabetes (OR per 5-year decrease 1.33; 95% CI 1.05-1.67, P = 0.016), presence of micro/macroalbuminuria (OR 0.34; 95% CI 0.15-0.78, P = 0.011), body weight reduction (OR per 1-kg decrease 1.11; 95% CI 1.02-1.21, P = 0.016), and HbA1c reduction (OR per 1% decrease 1.32; 95% CI 1.05-1.67, P = 0.019) were significantly associated with composite events of partial and complete CAN recovery. Age had the highest relative significance among the associated clinical factors. In addition, younger age was the only significant factor in complete CAN recovery. CONCLUSIONS: Younger age was the most important factor in CAN recovery in subjects with type 2 diabetes, including recovery from the definite or severe stage. HbA1c reduction, body weight reduction, no concurrent micro/macroalbuminuria, and shorter duration of diabetes were also significantly associated with CAN recovery.

Prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy: A prospective multicenter study.

OBJECTIVES: To estimate the prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy and to identify the high-risk groups. METHODS: From January 2015 to March 2016, rectal swabs of 557 men who underwent transrectal ultrasound-guided prostate needle biopsy were obtained from five institutions. Clinical variables, including demographics, rectal swab culture results and infectious complications, were evaluated. Univariable and multivariable analyses were used to identify the risk factors for fluoroquinolone resistance of rectal flora and infectious complications. RESULTS: The incidence of fluoroquinolone-resistant and extended-spectrum beta-lactamase production was 48.1 and 11.8%, respectively. The most common fluoroquinolone-resistant bacteria was Escherichia coli (81% of total fluoroquinolone-resistant bacteria, 39% of total rectal flora), and 16 (2.9%) patients had infectious complications. Univariable and multivariable analysis of clinical parameters affecting fluoroquinolone resistance showed no factor associated with fluoroquinolone resistance of rectal flora. The clinical parameter related to infectious complications after prostate biopsy was a history of operation within 6 months (relative risk 6.60; 95% confidence interval 1.99-21.8, P = 0.002). CONCLUSIONS: These findings suggest that a risk-based approach by history taking cannot predict antibiotic resistance of rectal flora, and physicians should consider targeted antibiotic prophylaxis or extended antibiotic prophylaxis for Korean patients undergoing transrectal ultrasound-guided prostate biopsy because of high antibiotic resistance of rectal flora.

Clarithromycin-based standard triple therapy can still be effective for Helicobacter pylori eradication in some parts of the Korea.

We evaluated the antibiotic resistance rates and eradication rates of clarithromycin based triple therapy from 2005 to 2010 retrospectively. In addition, we investigated the mechanism of clarithromycin resistance in Helicobacter pylori strains isolated from Korean patients. Two hundred and twelve strains of H. pylori were isolated from 204 patients. H. pylori ATCC 43504 was used as the standard strain. The eradication rates of H. pylori from 2005 to 2010 were 89.3%, 82.6%, 86.3%, 87.7%, 81.8%, and 84.2%, respectively. Total eradication rate was 84.9%. DNA sequences of the 23S RNA gene in clarithromycin-resistant strains were determined. The resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, moxifloxacin, and levofloxacin were 9.0%, 8.5%, 36.3%, 0%, 14.2%, 14.2%, and 14.2%, respectively. The multidrug resistance rate of H. pylori was 16.5%. Sequence analysis of clarithromycin-resistant strains showed an A2144G mutation in 8 of 14 strains (57.1%), a T2183C mutation in 5 of 14 strains (35.7%), and double mutations of both A2144G and T2183C in 1 of 14 strains (7.1%). In the present study, triple therapy may still be an effective eradication therapy for H. pylori infections in Korea. The A2144G and T2183C mutations are mainly present in clarithromycin-resistant isolates.

Silicosis caused by chronic inhalation of snail shell powder.

A 70-yr-old woman visited our hospital for shortness of breath. Chest CT showed ground glass opacity and traction bronchiectasis at right middle, lower lobe and left lingular division. Video-assisted thoracic surgical biopsy at right lower lobe and pathologic examination revealed mixed dust pneumoconiosis. Polarized optical microscopy showed lung lesions were consisted of silica and carbon materials. She was a housewife and never been exposed to silica dusts occupationally. She has taken freshwater snails as a health-promoting food for 40 yr and ground shell powder was piled up on her backyard where she spent day-time. Energy dispersive X-ray spectroscopy of snail shell and scanning electron microscopy with energy dispersive x-ray spectroscopy of lung lesion revealed that silica occupies important portion. Herein, we report the first known case of silicosis due to chronic inhalation of shell powder of freshwater snail.

A personalized blood glucose level prediction model with a fine-tuning strategy: A proof-of-concept study.

BACKGROUND: The accurate prediction of blood glucose (BG) level is still a challenge for diabetes management. This is due to various factors such as diet, personal physiological characteristics, stress, and activities influence changes in BG level. To develop an accurate BG level predictive model, we propose a personalized model based on a convolutional neural network (CNN) with a fine-tuning strategy. METHODS: We utilized continuous glucose monitoring (CGM) datasets from 1052 professional CGM sessions and split them into three groups according to type 1, type 2, and gestational diabetes mellitus (T1DM, T2DM, and GDM, respectively). During the preprocessing, only CGM data points were utilized, and future BG levels of four different prediction horizons (PHs, 15, 30, 45, and 60 min) were used as output. In training, we trained a general CNN and a multi-output random forest regressor using a hold-out method for each group. Next, we developed two personalized models: (1) by fine-tuning the general CNN on partial sample points of each CGM dataset, and (2) by learning a CNN from scratch on the points. RESULTS: For all groups, the fine-tuned CNN showed the lowest average root mean squared error, average mean absolute percentage error, highest average time gain (PH = 15 and 60 min in T1DM) and highest percentage in region A of Clarke error grid analysis at all PHs. In the performance comparison between the fine-tuned CNN and other models, we found that the fine-tuned CNN improved the performance of the general CNN in most cases and outperformed the scratch CNN at all PHs in all groups, making the fine-tuning strategy was useful for accurate BG level prediction. We analyzed all cases of four predictive patterns in each group, and found that the input BG level trend and the BG level at the time of prediction were related to the future BG level trend. CONCLUSIONS: We demonstrated the efficacy of the fine-tuning method in a large number of CGM datasets and analyzed the four predictive patterns. Therefore, we believe that the proposed method will significantly contribute to the development of an accurate personalized model and the analysis for its predictions.

Toward a Fully Automated Artificial Pancreas System Using a Bioinspired Reinforcement Learning Design: In Silico Validation.

OBJECTIVE: The automation of insulin treatment is the most challenge aspect of glucose management for type 1 diabetes owing to unexpected exogenous events (e.g., meal intake). In this article, we propose a novel reinforcement learning (RL) based artificial intelligence (AI) algorithm for a fully automated artificial pancreas (AP) system. METHODS: A bioinspired RL designing method was developed for automated insulin infusion. This method has reward functions that imply the temporal homeostatic objective and discount factors that reflect an individual specific pharmacological characteristic. The proposed method was applied to a training method using an RL algorithm and was evaluated in virtual patients from the FDA approved UVA/Padova simulator with unannounced meal intakes. RESULTS: For a single-meal experiment with preprandial fasting, the trained policy demonstrated fully automated regulation in both the basal and postprandial phases. In the in silico trial with a variation of insulin sensitivity and dawn phenomenon, the policy achieved a mean glucose of 124.72 mg/dL and percentage time in the normal range of 89.56%. The layer-wise relevance propagation provides interpretable information on AI-driven decision for robustness to sensor noise, automated postprandial regulation, and insulin stacking avoidance. CONCLUSION: The AP algorithm based on the bioinspired RL approach enables fully automated blood glucose control with unannounced meal intake. SIGNIFICANCE: The proposed framework can be extended to other drug-based treatments for systems with significant uncertainties.

Low Skeletal Muscle Mass Is Associated With the Presence, Incidence, and Progression of Coronary Artery Calcification.

BACKGROUND: Low skeletal muscle mass (SMM) is an emerging risk factor of cardiovascular disease (CVD). We investigated the association between SMM and coronary artery calcification (CAC). METHODS: We enrolled 19,728 adults free of CVD who underwent computed tomographic estimation of Agatston CAC scores for cross-sectional analysis. Among them, 5,401 subjects who had at least 2 follow-up CAC scores were included in longitudinal analysis. Relative SMM is presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/body weight (kg) × 100]. CAC presence and incidence were defined as CAC score > 0, and CAC progression was defined as √CAC score (follow-up) - √CAC score (baseline) > 2.5. RESULTS: Among all of the subjects (mean age 53.4 years, 80.8% male), the prevalence of CAC was 36.7%. The incidence of CAC was 17.4% during a mean of 3.6 years, and the progression of CAC was 49.9% during a mean of 2.3 years. The lowest SMI quartile was significantly associated with an increased risk of CAC presence (adjusted odds ratio 2.75, 95% confidence interval [CI] 2.45-3.05; P < 0.001), incidence (adjusted hazard ratio [AHR] 1.99, 95% CI 1.36-2.91; P < 0.001), and progression (AHR 1.48, 95% CI 1.25-1.77; P < 0.001) compared with the highest quartile. SMI as a continuous value was also significantly inversely associated with CAC. SMI was the best parameter to be related to CAC among other quantitative indices such as height or body mass index adjusted. CONCLUSIONS: Low SMM is significantly associated with an elevated risk of CAC, independently of other cardiometabolic parameters.

Association of Urinary N-Acetyl-ß-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-ß-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. METHODS: This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimate the severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. RESULTS: The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (ß=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. CONCLUSION: This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling.

BACKGROUND AND AIMS: Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side. METHODS: Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden's index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side. RESULTS: Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity. CONCLUSION: In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.

Association Between Continuous Glucose Monitoring-Derived Time in Range, Other Core Metrics, and Albuminuria in Type 2 Diabetes.

Background: As the use of continuous glucose monitoring (CGM) has increased, time in range (TIR) and other core CGM metrics are now emerging as the core metrics for clinical targets and assessing diabetic complications, beyond HbA1c. This study investigated the association between the CGM-derived TIR, hyperglycemia, hypoglycemia metrics, and albuminuria. Methods: A total of 866 subjects with type 2 diabetes who underwent 3 or 6 days of CGM and had urinary albumin-to-creatinine ratio (ACR) measurements were retrospectively reviewed. CGM metrics were defined according to the most recent international consensus. Albuminuria was defined as one or more of the ACR measurements being >30 mg/g. Results: The overall prevalence of albuminuria was 36.6%. The prevalence of albuminuria was lower in subjects who achieved the target of TIR 70-180 mg/dL, time above range (TAR) >180 mg/dL, and TAR >250 mg/dL, as recommended by international consensus (P < 0.001). Multiple logistic regression analysis revealed that the odds ratio of having albuminuria was 0.94 (95% confidence interval: 0.88-0.99, P for trend = 0.04) per 10% increase in TIR of 70-180 mg/dL, after adjusting for multiple factors, including glycemic variability. The results were similar for hyperglycemia metrics (TAR >250 mg/dL and TAR >180 mg/dL). Conclusions: TIR 70-180 mg/dL and hyperglycemia metrics are strongly associated with albuminuria in type 2 diabetes.

Effects of low skeletal muscle mass and sarcopenic obesity on albuminuria: a 7-year longitudinal study.

We aimed to identify the association between low skeletal muscle, sarcopenic obesity, and the incidence of albuminuria in the general population using a longitudinal study. Data from 29,942 subjects who underwent two or more routine health examinations from 2006 to 2013 were retrospectively reviewed. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass estimated by bioelectrical impedance analysis. The cumulative incidence of albuminuria was 981 (3.3%) during the 7-year follow-up period. The hazard ratio of incident albuminuria was 1.44 (95% CI: 1.22-1.71, p for trend <0.001) in the lowest SMI tertile relative to the highest SMI tertile after multivariable adjustment. After additionally adjusting for general and central obesity, the hazard ratio was 1.35 (95% CI: 1.13-1.61, p for trend = 0.001) and 1.30 (95% CI: 1.08-1.56, p for trend = 0.003), respectively. Furthermore, the risk of developing albuminuria was much higher in the sarcopenic obesity group (HR: 1.49, 95% CI: 1.21-1.81, p for trend <0.001) compared to the other groups. Sarcopenic obesity, as well as low skeletal muscle, may lead to albuminuria in general populations.

An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment.

BACKGROUND: We aimed to describe the outcome of a computerized intravenous insulin infusion (CII) protocol integrated to the electronic health record (EHR) system and to improve the CII protocol in silico using the EHR-based predictors of the outcome. METHODS: Clinical outcomes of the patients who underwent the CII protocol between July 2016 and February 2017 and their matched controls were evaluated. In the CII protocol group (n=91), multivariable binary logistic regression analysis models were used to determine the independent associates with a delayed response (taking ≥6.0 hours for entering a glucose range of 70 to 180 mg/dL). The CII protocol was adjusted in silico according to the EHR-based parameters obtained in the first 3 hours of CII. RESULTS: Use of the CII protocol was associated with fewer subjects with hypoglycemia alert values (P=0.003), earlier (P=0.002), and more stable (P=0.017) achievement of a glucose range of 70 to 180 mg/dL. Initial glucose level (P=0.001), change in glucose during the first 2 hours (P=0.026), and change in insulin infusion rate during the first 3 hours (P=0.029) were independently associated with delayed responses. Increasing the insulin infusion rate temporarily according to these parameters in silico significantly reduced delayed responses (P<0.0001) without hypoglycemia, especially in refractory patients. CONCLUSION: Our CII protocol enabled faster and more stable glycemic control than conventional care with minimized risk of hypoglycemia. An EHR-based adjustment was simulated to reduce delayed responses without increased incidence of hypoglycemia.

Systemic amyloidosis manifested by gastric outlet obstruction.

Amyloidosis is characterized by extracellular deposition of insoluble protein fibrils that stain with Congo red application and appear apple green under polarized light. The presenting symptoms result from the involvement of many affected, nonspecific and generalized organ systems. Our patient was an 80-year-old woman with no medical history. She presented with a 2-week history of nausea and vomiting. An esophagogastroduodenoscopy showed erythematous and edematous mucosa on the antrum with pyloric stenosis. Histopathologic examination of the biopsy specimen showed the deposition of amorphous, homogeneous, and acidophilic material in the gastric mucosa. Amyloidal protein was proven by positive Congo red stain. A serum and urine immunfixation electrophoresis showed lambda light chain band. She developed symptoms of repeated greenish color vomiting. A follow-up esophagogastroduodenoscopy showed progressed antral obstruction. However, she refused further evaluation and treatment and was managed conservatively. She later died of disease progression after 34 hospital days.

Association of Polymorphisms in the Prostate-Specific Antigen (PSA) Gene Promoter with Serum PSA Level and PSA Changes after Dutasteride Treatment in Korean Men with Benign Prostatic Hypertrophy.

PURPOSE: Studies of genetic variation in the prostate-specific antigen (PSA) gene have improved the diagnostic accuracy of PSA for diagnosing prostate diseases in Caucasians. However, the reference ranges and pharmacokinetics of PSA differ significantly according to race. Therefore, we evaluated the association between genetic variations in the PSA promoter area and benign prostatic hyperplasia (BPH) phenotypes in Korean BPH patients. MATERIALS AND METHODS: One hundred twenty-one men were enrolled. The initial serum PSA level, prostate size, and PSA changes at 3 months after treatment with dutasteride were determined. We amplified the promoter region of the PSA gene (nucleotide positions -158 to -356 and -5217 to -5429) and sequenced the products. RESULTS: Three relatively well characterized single-nucleotide polymorphisms (SNPs; rs3760722, rs266867, and rs266868), six uncharacterized SNPs (rs17554958, rs266882, rs4802754, rs2739448, rs2569733, and rs17526278), and one novel SNP (nucleotide position -5402) were found. There were no statistically significant correlations between any of the SNPs of the PSA promoter area and age-adjusted prostate sizes, initial PSA levels, or PSA variations after 3 months of dutasteride treatment. CONCLUSIONS: SNPs in the PSA promoter area were not associated with BPH phenotypes. We could not predict serum PSA changes after dutasteride treatment on the basis of PSA promoter genotype in Korean patients with BPH.