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1. Serial Fibroblast Growth Factor 23 Measurements and Risk of Requirement for Kidney Replacement Therapy: The CRIC (Chronic Renal Insufficiency Cohort) Study

Author

Mehta, Rupal, Cai, Xuan, Lee, Jungwha, Xie, Dawei, Wang, Xue, Scialla, Julia, Anderson, Amanda H, Taliercio, Jon, Dobre, Mirela, Chen, Jing, Fischer, Michael, Leonard, Mary, Lash, James, Hsu, Chi-yuan, de Boer, Ian H, Feldman, Harold I, Wolf, Myles, Isakova, Tamara, Investigators, CRIC Study, Appel, Lawrence J, Go, Alan S, He, Jiang, Rao, Panduranga S, Rahman, Mahboob, and Townsend, Raymond R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Kidney Disease, Clinical Research, Renal and urogenital, Biomarkers, Cohort Studies, Disease Progression, Female, Fibroblast Growth Factor-23, Fibroblast Growth Factors, Humans, Kaplan-Meier Estimate, Kidney Failure, Chronic, Kidney Transplantation, Male, Middle Aged, Proportional Hazards Models, Renal Insufficiency, Chronic, Renal Replacement Therapy, Risk Assessment, Risk Factors, United States, CRIC Study Investigators, CKD progression, Chronic kidney disease, biomarker, dialysis, disease trajectory, end-stage renal disease, fibroblast growth factor 23, kidney failure, kidney function decline, renal replacement therapy, transplant, Public Health and Health Services, Urology & Nephrology, Clinical sciences
Abstract

Rationale & objectiveStudies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses.Study designCase-cohort study.Setting & participantsTo evaluate the association between serial FGF-23 levels and risk for requiring KRT, our primary analysis included 1,597 individuals in the Chronic Renal Insufficiency Cohort Study who had up to 5 annual measurements of carboxy-terminal FGF-23. There were 1,135 randomly selected individuals, of whom 266 initiated KRT, and 462 individuals who initiated KRT outside the random subcohort.ExposureSerial FGF-23 measurements and FGF-23 trajectory group membership.OutcomesIncident KRT.Analytical approachTo handle time-dependent confounding, our primary analysis of time-updated FGF-23 levels used time-varying inverse probability weighting in a discrete time failure model. To compare our results with prior data, we used baseline and time-updated FGF-23 values in weighted Cox regression models. To examine the association of FGF-23 trajectory subgroups with risk for incident KRT, we used weighted Cox models with FGF-23 trajectory groups derived from group-based trajectory modeling as the exposure.ResultsIn our primary analysis, the HR for the KRT outcome per 1 SD increase in the mean of natural log-transformed (ln)FGF-23 in the past was 1.94 (95% CI, 1.51-2.49). In weighted Cox models using baseline and time-updated values, elevated FGF-23 level was associated with increased risk for incident KRT (HRs per 1 SD ln[FGF-23] of 1.18 [95% CI, 1.02-1.37] for baseline and 1.66 [95% CI, 1.49-1.86] for time-updated). Membership in the slowly and rapidly increasing FGF-23 trajectory groups was associated with ∼3- and ∼21-fold higher risk for incident KRT compared to membership in the stable FGF-23 trajectory group.LimitationsResidual confounding and lack of intact FGF-23 values.ConclusionsIncreasing FGF-23 levels are independently associated with increased risk for incident KRT.

Published
2020

2. Serum Calcification Propensity and Coronary Artery Calcification Among Patients With CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study

Author

Bundy, Joshua D, Cai, Xuan, Scialla, Julia J, Dobre, Mirela A, Chen, Jing, Hsu, Chi-yuan, Leonard, Mary B, Go, Alan S, Rao, Panduranga S, Lash, James P, Townsend, Raymond R, Feldman, Harold I, de Boer, Ian H, Block, Geoffrey A, Wolf, Myles, Smith, Edward R, Pasch, Andreas, Isakova, Tamara, Investigators, CRIC Study, Appel, Lawrence J, He, Jiang, and Rahman, Mahboob

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Kidney Disease, Atherosclerosis, Heart Disease, Cardiovascular, Prevention, Heart Disease - Coronary Heart Disease, Renal and urogenital, Good Health and Well Being, Age Factors, Aged, Cohort Studies, Comorbidity, Coronary Artery Disease, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Propensity Score, Prospective Studies, Renal Insufficiency, Chronic, Sex Factors, Survival Analysis, Vascular Calcification, CRIC Study Investigators, Coronary artery disease, calcification propensity, calciprotein particles, cardiovascular disease, chronic kidney disease, coronary artery calcium, epidemiology, risk factors, transformation time (T(50)), Clinical Sciences, Public Health and Health Services, Urology & Nephrology, Clinical sciences
Abstract

RATIONALE & OBJECTIVE:Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to 4. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n=1,274) and follow-up (n=780) CAC measurements. PREDICTORS:Calcification propensity, quantified as transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. Covariates included age, sex, race/ethnicity, clinical site, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, number of antihypertensive medications, current smoking, history of cardiovascular disease, total cholesterol level, and use of statin medications. OUTCOMES:CAC prevalence, severity, incidence, and progression. ANALYTICAL APPROACH:Multivariable-adjusted generalized linear models. RESULTS:At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T50 was not associated with CAC prevalence but was significantly associated with greater CAC severity among participants with prevalent CAC: 1-SD lower T50 was associated with 21% (95% CI, 6%-38%) greater CAC severity. Among 780 participants followed up an average of 3 years later, 65 (20%) without baseline CAC developed incident CAC, while 89 (19%) with baseline CAC had progression, defined as annual increase≥100 Agatston units. After multivariable adjustment, T50 was not associated with incident CAC but was significantly associated with CAC progression: 1-SD lower T50 was associated with 28% (95% CI, 7%-53%) higher risk for CAC progression. LIMITATIONS:Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification. CONCLUSIONS:Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression.

Published
2019

3. Racial/Ethnic Differences in Left Ventricular Structure and Function in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

Author

Ahmad, Faraz S, Cai, Xuan, Kunkel, Katherine, Ricardo, Ana C, Lash, James P, Raj, Dominic S, He, Jiang, Anderson, Amanda H, Budoff, Matthew J, Wright Nunes, Julie A, Roy, Jason, Wright, Jackson T, Go, Alan S, St John Sutton, Martin G, Kusek, John W, Isakova, Tamara, Wolf, Myles, and Keane, Martin G

Subjects
Hypertension, Prevention, Clinical Research, Cardiovascular, Kidney Disease, Renal and urogenital, Good Health and Well Being, Adult, Aged, Blacks, Blood Pressure, Cohort Studies, Cross-Sectional Studies, Electrocardiography, Ethnicity, Female, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Male, Middle Aged, Prevalence, Renal Insufficiency, Chronic, Socioeconomic Factors, Ventricular Dysfunction, Left, Ventricular Remodeling, Whites, Young Adult, blood pressure, echocardiography, hypertension, left ventricular hypertrophy, race and ethnicity, remodeling, renal insufficiency, CRIC Study Investigators, White People, Black People, Clinical Sciences, Cardiovascular System & Hematology
Abstract

BackgroundChronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD.MethodsIn a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors.ResultsWe identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69).ConclusionIn a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients.

Published
2017

4. Associations of FGF23 With Change in Bone Mineral Density and Fracture Risk in Older Individuals

Author

Isakova, Tamara, Cai, Xuan, Lee, Jungwha, Katz, Ronit, Cauley, Jane A, Fried, Linda F, Hoofnagle, Andrew N, Satterfield, Suzanne, Harris, Tamara B, Shlipak, Michael G, Sarnak, Mark J, Ix, Joachim H, and Study, for the Health ABC

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Aging, Clinical Research, Osteoporosis, Musculoskeletal, Aged, Bone Density, Female, Fibroblast Growth Factor-23, Fibroblast Growth Factors, Follow-Up Studies, Fractures, Bone, Glomerular Filtration Rate, Humans, Male, Parathyroid Hormone, Renal Insufficiency, Chronic, Risk Factors, FIBROBLAST GROWTH FACTOR 23, BONE MINERAL DENSITY, FRACTURE, CHRONIC KIDNEY DISEASE, Health ABC Study, Biological Sciences, Engineering, Medical and Health Sciences, Anatomy & Morphology, Biological sciences, Biomedical and clinical sciences
Abstract

Elevated levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) have been linked to greater risk of fractures in some studies, especially among individuals with chronic kidney disease (CKD). We evaluated FGF23 as a risk factor for bone loss and fractures in the Health, Aging, and Body Composition (Health ABC) study, which is a prospective biracial cohort of well-functioning adults aged 70 to 79 years recruited at two clinical centers in the United States. The sample for the bone mineral density (BMD) analyses consisted of 2234 participants who had at least two serial total hip areal BMD measures. The fracture analyses included 2786 participants, 567 of whom sustained a fracture during a median follow up of 4.95 years. Linear mixed-effects models were used for longitudinal measurements of total hip areal BMD and the proportional subdistribution hazard regression model subject to competing risks of death was used for risk of fracture. The median FGF23 was 46.7 (interquartile range [IQR] 36.7 to 60.2) pg/mL. The mean annualized percent change in total hip areal BMD did not vary significantly according to FGF23 quartile in all participants (p for trend = 0.70), but the effect was modified by CKD status (adjusted p for interaction

Published
2016

5. Cognitive-behavioral therapy in depressed primary care patients with co-occurring problematic alcohol use: effect of telephone-administered vs. face-to-face treatment-a secondary analysis.

Author

Kalapatapu, Raj K, Ho, Joyce, Cai, Xuan, Vinogradov, Sophia, Batki, Steven L, and Mohr, David C

Subjects
Humans, Alcoholism, Diagnosis, Dual (Psychiatry), Treatment Outcome, Depression, Patient Compliance, Psychiatric Status Rating Scales, Telemedicine, Time Factors, Telephone, Adult, Middle Aged, Office Visits, Primary Health Care, Female, Male, Cognitive Behavioral Therapy, alcohol, depressed, face-to-face, primary care, telephone, Clinical Research, Brain Disorders, Substance Misuse, Behavioral and Social Science, Clinical Trials and Supportive Activities, Rehabilitation, Alcoholism, Alcohol Use and Health, Mental Health, Evaluation of treatments and therapeutic interventions, 6.6 Psychological and behavioural, Mental health, Good Health and Well Being, Public Health and Health Services, Psychology, Substance Abuse
Abstract

This secondary analysis of a larger study compared adherence to telephone-administered cognitive-behavioral therapy (T-CBT) vs. face-to-face CBT and depression outcomes in depressed primary care patients with co-occurring problematic alcohol use. To our knowledge, T-CBT has never been directly compared to face-to-face CBT in such a sample of primary care patients. Participants were randomized in a 1:1 ratio to face-to-face CBT or T-CBT for depression. Participants receiving T-CBT (n = 50) and face-to-face CBT (n = 53) were compared at baseline, end of treatment (week 18), and three-month and six-month follow-ups. Face-to-face CBT and T-CBT groups did not significantly differ in age, sex, ethnicity, marital status, educational level, severity of depression, antidepressant use, and total score on the Alcohol Use Disorders Identification Test. Face-to-face CBT and T-CBT groups were similar on all treatment adherence outcomes and depression outcomes at all time points. T-CBT and face-to-face CBT had similar treatment adherence and efficacy for the treatment of depression in depressed primary care patients with co-occurring problematic alcohol use. When targeting patients who might have difficulties in accessing care, primary care clinicians may consider both types of CBT delivery when treating depression in patients with co-occurring problematic alcohol use.

Published
2014

6. RUNX3 methylation and expression associated with advanced precancerous gastric lesions in a Chinese population

Author

Wei-Cheng You, Yang Zhang, Lian Zhang, Ji-You Li, Tong Zhou, Cai-Xuan Dong, Kai-Feng Pan, Jun-Ling Ma, and Wen-Qing Li

Subjects
Adult, Gastritis, Atrophic, Male, Cancer Research, medicine.medical_specialty, Atrophic gastritis, Population, Polymerase Chain Reaction, Gastroenterology, Helicobacter Infections, Cohort Studies, Immunoenzyme Techniques, Asian People, Stomach Neoplasms, Internal medicine, medicine, Humans, education, education.field_of_study, Helicobacter pylori, business.industry, Intestinal metaplasia, Cancer, DNA, Neoplasm, General Medicine, Odds ratio, Methylation, DNA Methylation, Middle Aged, medicine.disease, digestive system diseases, Core Binding Factor Alpha 3 Subunit, Gastric Mucosa, Dysplasia, Immunohistochemistry, Female, business, Precancerous Conditions
Abstract

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of gastric cancer. Our study aimed to investigate the correlation of RUNX3 methylation, expression and the risk of advanced gastric lesions, based on a high-risk population in Linqu County, Shandong Province, China. Methylation status of RUNX3 was determined by methylation-specific polymerase chain reaction, and expression was detected by immunohistochemical analysis in 1113 subjects with different gastric lesions. Results showed that the frequency of RUNX3 methylation was significantly increased in subjects with advanced gastric lesions. The odds ratios (ORs) were 2.09 [95% confidence interval (CI): 1.49―2.94] for intestinal metaplasia (IM), 3.22 (95% CI: 2.33―4.47) for indefinite dysplasia (Ind DYS) and 2.03 (95% CI: 1.23―3.37) for dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. Stratified analysis indicated that the frequency of RUNX3 methylation was higher in subjects with Helicobacter pylori infection (OR, 2.74; 95% CI: 2.00―3.76). Moreover, there was a reverse grade-response relationship between the level of RUNX3 expression and risk of gastric lesions. Among subjects with mild, moderate or heavy expression, the risk was decreased by 41, 59 or 80% for IM (P trend < 0.0001); 40, 64 or 74% for Ind DYS (P trend < 0.0001) and 28, 59 or 51 % for DYS (P trend = 0.045), respectively. Furthermore, RUNX3 expression was negatively associated with increased frequency of RUNX3 methylation (OR, 0.76; 95% CI: 0.59―0.98). These findings suggest that RUNX3 may play important roles in the development of advanced gastric lesions.

Published
2010
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7. Promoter methylation ofp16associated withHelicobacter pyloriinfection in precancerous gastric lesions: A population-based study

Author

Cai-Xuan Dong, Yang Zhang, Dajun Deng, Jing Zhou, Lian Zhang, Wei-Cheng You, and Kai-Feng Pan

Subjects
Male, China, Cancer Research, medicine.medical_specialty, Atrophic gastritis, Population, Biology, Gastroenterology, Helicobacter Infections, Stomach Neoplasms, Internal medicine, medicine, Gastric mucosa, Humans, Promoter Regions, Genetic, education, Stomach cancer, Cyclin-Dependent Kinase Inhibitor p16, Aged, education.field_of_study, Helicobacter pylori, Genes, p16, Intestinal metaplasia, Methylation, DNA Methylation, Middle Aged, medicine.disease, biology.organism_classification, medicine.anatomical_structure, Oncology, Gastric Mucosa, Dysplasia, Gastritis, Immunology, CpG Islands, Female, Precancerous Conditions
Abstract

To investigate the relationship between p16 methylation and Helicobacter pylori infection in precancerous gastric lesions, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer in China. Methylation status of p16 was evaluated by methylation-specific polymerase chain reaction in 920 subjects with precancerous gastric lesions. H. pylori status was determined by 13C-urea breath test and the density of H. pylori in biopsy specimens used for detecting methylation status was assessed by the modified Giemsa stain. The frequency of p16 methylation was significantly higher in subjects with H. pylori positive than those with H. pylori negative in each category of gastric lesion (p < 0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs) of p16 methylation were markedly elevated in subjects with H. pylori positive for superficial gastritis (OR, 9.45; 95% confidence interval [CI]: 2.94–30.41), chronic atrophic gastritis (OR, 15.92; 95%CI: 7.60–33.36), intestinal metaplasia (OR, 4.46; 95%CI: 2.44–8.13), indefinite dysplasia (OR, 3.67; 95%CI: 1.90–7.10), and dysplasia (OR, 2.48; 95%CI: 1.02–5.99). Moreover, the frequencies of p16 methylation increased steadily with the severity of H. pylori density in gastric mucosa. Compared with H. pylori negative, the OR of p16 methylation was 1.02–16.13 times higher in subjects with mild H. pylori infection, and 2.69–38.73 times higher in those with moderate/severe infection, respectively. Our findings indicate that p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island. © 2008 Wiley-Liss, Inc.

Published
2009
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8. Associations of FGF23 with change in bone mineral density and fracture risk in older individuals

Author

Isakova, Tamara, Cai, Xuan, Lee, Jungwha, Katz, Ronit, Cauley, Jane A., Fried, Linda F., Hoofnagle, Andrew N., Satterfield, Suzanne, Harris, Tamara B., Shlipak, Michael G., Sarnak, Mark J., and Ix, Joachim H.

Subjects
musculoskeletal diseases, Male, urologic and male genital diseases, Article, Fibroblast Growth Factors, stomatognathic diseases, Fibroblast Growth Factor-23, Fractures, Bone, Bone Density, Parathyroid Hormone, Risk Factors, Humans, Female, Renal Insufficiency, Chronic, Aged, Follow-Up Studies, Glomerular Filtration Rate
Abstract

Elevated levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) have been linked to greater risk of fractures in some studies, especially among individuals with chronic kidney disease (CKD). We evaluated FGF23 as a risk factor for bone loss and fractures in the Health, Aging, and Body Composition (Health ABC) study, which is a prospective biracial cohort of well-functioning adults aged 70 to 79 years recruited at two clinical centers in the United States. The sample for the bone mineral density (BMD) analyses consisted of 2234 participants who had at least two serial total hip areal BMD measures. The fracture analyses included 2786 participants, 567 of whom sustained a fracture during a median follow up of 4.95 years. Linear mixed-effects models were used for longitudinal measurements of total hip areal BMD and the proportional subdistribution hazard regression model subject to competing risks of death was used for risk of fracture. The median FGF23 was 46.7 (interquartile range [IQR] 36.7 to 60.2) pg/mL. The mean annualized percent change in total hip areal BMD did not vary significantly according to FGF23 quartile in all participants (p for trend = 0.70), but the effect was modified by CKD status (adjusted p for interaction0.001). Among participants with CKD, the unadjusted mean annualized percent change in total hip areal BMD was greater with higher levels of FGF23 (unadjusted p for trend = 0.02), but the trend was attenuated with adjustment for estimated glomerular filtration rate and parathyroid hormone (adjusted p for trend = 0.30). FGF23 was not significantly associated with fracture risk in crude (hazard ratio [HR] per doubling of FGF23, 0.97; 95% CI, 0.85 to 1.12) or adjusted models (HR per doubling of FGF23, 1.02; 95% CI, 0.86 to 1.22), and these findings were not modified by gender or CKD status. FGF23 levels are not associated with bone loss or fracture risk in older adults with low prevalence of CKD.

Published
2015

9. Genetic Variants in Cyclooxygenase-2: Expression and Risk of Gastric Cancer and Its Precursors in a Chinese Population

Author

Cai-Xuan Dong, Kai-Feng Pan, Dongxin Lin, Yang Zhang, Lian Zhang, Fen Liu, Lin Shen, Dajun Deng, Xuemei Zhang, Ji-You Li, Jun-Ling Ma, and Wei-Cheng You

Subjects
Adult, Male, China, medicine.medical_specialty, Genotype, Atrophic gastritis, Molecular Sequence Data, Population, Biology, Polymerase Chain Reaction, Risk Assessment, Gastroenterology, Helicobacter Infections, Denaturing high performance liquid chromatography, Age Distribution, Stomach Neoplasms, Internal medicine, Biopsy, Confidence Intervals, Odds Ratio, Prevalence, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Sex Distribution, education, Neoplasm Staging, education.field_of_study, Base Sequence, Hepatology, medicine.diagnostic_test, Genetic Variation, Cancer, Odds ratio, Middle Aged, medicine.disease, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Cross-Sectional Studies, Cyclooxygenase 2, Dysplasia, Immunology, Female, Precancerous Conditions
Abstract

Background & Aims: To screen the genetic variants in cyclooxygenase-2 (COX-2), and evaluate their effects on COX-2 expression and risk of gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shangdong Province, an area of China, a high-risk area of GC. Methods: Genotypes were determined by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography analysis in 248 GC cases and 1523 subjects with precancerous gastric lesions. COX-2 expression was detected by immunohistochemical analysis of biopsy specimens of 593 subjects selected at random from 1523 subjects. COX-2 transcriptional activity was examined by luciferase reporter gene assay. Results: We found an increased risk of GC in subjects with 1195 AA genotype (adjusted odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.45–3.75). Stratified analysis indicated that an elevated risk of GC was observed in subjects carrying the AA genotype and Helicobacter pylori infection (OR, 3.88; 95% CI: 1.46 –10.34) or smoking (OR, 7.02; 95% CI: 2.19 –22.48), and a high expression of COX-2 was found in subjects with AA genotype (OR, 1.84; 95% CI: 1.09 – 3.10) compared with GG genotype. The prevalence of COX-2 expression positivity varied markedly by histologic status, and the OR (OR, 5.35; 95% CI: 2.64 –10.8) was significantly increased for dysplasia compared with superficial gastritis/chronic atrophic gastritis. Furthermore, tissue homogenate with H pylori infection could significantly stimulate COX-2 promoter activity driven by 1195A compared with the 1195G containing counterparts. Conclusions: These findings suggest that COX-2 polymorphisms may play an important role, at least in part, in developing GC in this high-risk population.

Published
2006
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10. Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas

Author

Xian-Zi Wen, Liankun Gu, Bu-Dong Zhu, Jing Zhou, Wei-Cheng You, Jiafu Ji, Zhaojun Liu, Kai-Feng Pan, Dajun Deng, Zheming Lu, Cai-Xuan Dong, and Yoshimitsu Akiyama

Subjects
Adult, Male, Pathology, medicine.medical_specialty, GATA5 Transcription Factor, Helicobacter Infections, Stomach Neoplasms, Gastric mucosa, medicine, Humans, Stomach cancer, Promoter Regions, Genetic, Aged, Aged, 80 and over, biology, Helicobacter pylori, Stomach, digestive, oral, and skin physiology, Carcinoma, Gastroenterology, General Medicine, Methylation, DNA Methylation, Middle Aged, biology.organism_classification, medicine.disease, Molecular biology, digestive system diseases, Gastric Intraepithelial Neoplasia, GATA4 Transcription Factor, Gastric Dysplasia, medicine.anatomical_structure, DNA methylation, embryonic structures, Original Article, CpG Islands, Female
Abstract

AIM: To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis. METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired sporadic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP) and confirmed by denatured high performance liquid chromatography (DHPLC). Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori) infection was analyzed. RESULTS: GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively) and their corresponding normal tissues (41.3% and 46.3%) by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01). Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0%) and indefinite for dysplasia (42.9% and 46.7%), respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5%) and 3/39 (7.7%) of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P = 0.023 and 0.027, two-sides). CONCLUSION: Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early frequent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.

Published
2010

11. [The correlative analysis of indefinite dysplasia and dysplasia, and its p16 methylation in human gastric mucosa with Helicobacter pylori infection]

Author

Cai Xuan, Dong, Da Jun, Deng, Jing, Zhou, Lian, Zhang, Jun Ling, Ma, Kai Feng, Pan, and Wei Cheng, You

Subjects
Adult, Male, Helicobacter pylori, Genes, p16, DNA Methylation, Middle Aged, Helicobacter Infections, Gastric Mucosa, Stomach Neoplasms, Humans, CpG Islands, Female, Promoter Regions, Genetic, Precancerous Conditions, Aged
Abstract

To compare the CpG island methylation status of p16 in subjects with gastric indefinite dysplasia or dysplasia, and investigate its association with exposure factors.Methylation status of p16 was determined by methylation specific PCR method and denaturing high-performance liquid chromatography analysis in 223 indefinite dysplasia and 130 dysplasia from Linqu County in Shandong Province, an area with high GC mortality rates. Multivariable analysis was used to analyze the relationship between p16 methylation and age, gender, cigarette smoking, alcohol drinking, and Helicobacter pylori infection.The methylation frequency of p16 in indefinite dysplasia was not significantly different from that of dysplasia (28.3% vs 24.6%, P=0.46). No significant association was found between p16 methylation and age, gender, cigarette smoking, and alcohol drinking. In dysplasia, the association between p16 methylation and Helicobacter pylori infection was close to the statistical significance by univariate analysis that the relative risk of p16 methylation of the infected subjects(n=93) is higher than that of the uninfected subjects (n=37)(OR=2.62, 95% CI: 0.92 to 7.43, P=0.07).But by multivariate analysis, there was no association between them(P=0.11).The frequency of p16 methylation in gastric mucosa of indefinite dysplasia was similar to that of dysplasia. p16 methylation status was not associated with age, but might be significantly associated with Helicobacter pylori infection.

Published
2008

12. Lifetime Risk for Heart Failure Among White and Black Americans Cardiovascular Lifetime Risk Pooling Project

Author

Huffman, Mark D., Berry, Jarett D., Ning, Hongyan, Dyer, Alan R., Garside, Daniel B., Cai, Xuan, Daviglus, Martha L., and Lloyd-Jones, Donald M.

Subjects
Adult, Male, Time Factors, Adolescent, heart failure, Kaplan-Meier Estimate, Risk Assessment, Severity of Illness Index, Article, White People, Body Mass Index, Cohort Studies, Young Adult, Sex Factors, Predictive Value of Tests, Humans, Aged, Anthropometry, Age Factors, Middle Aged, Prognosis, lifetime risk, Health Surveys, Survival Analysis, United States, Black or African American, Cardiovascular Diseases, Female, epidemiology
Abstract

ObjectivesThis study sought to estimate lifetime risk for heart failure (HF) by sex and race.BackgroundPrior estimates of lifetime risk for developing HF range from 20% to 33% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made.MethodsUsing public-release and internal datasets from National Heart, Lung, and Blood Institute–sponsored cohorts, we estimated lifetime risks for developing HF to age 95 years, with death free of HF as the competing event, among participants in the CHA (Chicago Heart Association Detection Project in Industry), ARIC (Atherosclerosis Risk in Communities), and CHS (Cardiovascular Health Study) cohorts.ResultsThere were 39,578 participants (33,652 [85%] white; 5,926 [15%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30% to 42% in white men, 20% to 29% in black men, 32% to 39% in white women, and 24% to 46% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher blood pressure and body mass index at all ages in both blacks and whites, and did not diminish substantially with advancing index age.ConclusionsThese are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.

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