Review on the Recent Advances on Typhoid Vaccine Development and Challenges Ahead.

Control of Salmonella enterica serovar typhi (S. typhi), the agent of typhoid fever, continues to be a challenge in many low- and middle-income countries. The major transmission route of S. typhi is fecal-oral, through contaminated food and water; thus, the ultimate measures for typhoid fever prevention and control include the provision of safe water, improved sanitation, and hygiene. Considering the increasing evidence of the global burden of typhoid, particularly among young children, and the long-term horizon for sustained, effective water and sanitation improvements in low-income settings, a growing consensus is to emphasize preventive vaccination. This review provides an overview of the licensed typhoid vaccines and vaccine candidates under development, and the challenges ahead for introduction.

WHO implementation workshop on guidelines on procedures and data requirements for changes to approved biotherapeutic products, Seoul, Republic of Korea, 25-26 June 2019.

The first global workshop on implementation of the WHO guidelines on procedures and data requirements for changes to approved biotherapeutic products adopted by the WHO Expert Committee in 2018 was held in June 2019. The workshop participants recognized that the principles based on sound science and the potential for risk, as described in the WHO Guidelines on post-approval changes, which constitute the global standard for product life-cycle management are providing clarity and helping national regulatory authorities in establishing guidance while improving time-lines for an efficient regulation of products. Consequently, the regulatory situation for post-approval changes and guideline implementation is changing but there is a disparity between different countries. While the guidelines are gradually being implemented in some countries and also being considered in other countries, the need for regional workshops and further training on post-approval changes was a common theme reiterated by many participants. Given the complexities relating to post-approval changes in different regions/countries, there was a clear understanding among all participants that an efficient approach for product life-cycle management at a national level is needed to ensure faster availability of high standard, safe and efficacious medicines to patients as per the World Health Assembly Resolution 67.21.

Control of clonorchiasis in Korea: effectiveness of health education for community leaders and individuals in an endemic area.

OBJECTIVES: To develop effective intervention programmes to control Clonorchis sinensis infection, three interventions were evaluated in a clonorchiasis-endemic area of Korea. METHODS: Four thousand two hundred and sixty-seven voluntary participants in Sancheong county were tested at baseline and two follow-up surveys after 1 and 3 years. Faecal samples were examined for C. sinensis eggs using the Kato-Katz method. Participants were divided into three intervention groups by areas and year recruited: national prevention programme only (mass health campaign and praziquantel treatment) for Group A; health education for community leaders added for Group B; and individual health education added for Group C. RESULTS: The prevalence of C. sinensis infection fell substantially in all three intervention groups between baseline and 3-year follow-up: from 31.1% to 14.9% in Group A, from 29.6% to 6.8% in Group B and from 21.9% to 8.6% in Group C. The control effectiveness was highest in Group B with 76.8%. The new infection rate was 16.3%, 12.8% and 7.6% in Group A, B and C, respectively. The reinfection rate was lower in Group B (3.8%) than Group C (12.2%). CONCLUSIONS: To control C. sinensis infection in endemic areas of Korea, health education for community leaders or individuals on prevention of C. sinensis infection should be added to national control programmes.

Seasonal influenza vaccination: A global review of national policies in 194 WHO member states in 2022.

INTRODUCTION: Seasonal influenza vaccination prevents severe influenza disease and death. The World Health Organization (WHO) encourages all countries to consider annual seasonal influenza vaccination for health workers, people with chronic conditions, older adults, pregnant women and other high-risk populations as relevant for their national context. This paper provides a global update on the status of countries' influenza vaccination policies and programmes as of December 2022. METHODS: We analysed the WHO-UNICEF (United Nations Children's Fund) Joint Reporting Form on Immunization's influenza vaccine-related data. We used STATA 17 to conduct descriptive analyses of reported seasonal influenza vaccine availability and seasonal influenza vaccination policies globally. RESULTS: Seasonal influenza vaccine doses were available in 74 % of WHO Member States (143/194) in 2022. Fewer countries, 66 % of WHO Member States (128/194), had a seasonal influenza vaccination policy, of which 68 countries reported having a policy for the public sector, 53 for the public and private sectors, two for the private sector only, and five did not report the sector. More than half of WHO Member States (100 countries) recommend annual seasonal influenza vaccination for all four of the WHO recommended priority groups. Influenza vaccination coverage data were reported by 64 countries; globally the median coverage rates varied by group: 37 % for pregnant women, 55 % for older adults and 62 % for health workers. DISCUSSION: The number of countries using seasonal influenza vaccines has grown over time, but there is still opportunity for continued development and strengthening of national programmes, particularly in low- and middle-income countries (LMICs). To support countries, WHO is providing technical guidance and resources to enable better reporting of influenza vaccination data. More complete and higher quality data will help countries and global health stakeholders to support national decision-making and programme strengthening. Where available, WHO encourages countries to co-administer influenza and COVID-19 vaccination to increase programmatic efficiency and coverage of both vaccines among recommended groups.

Responding to COVID-19 vaccine-related safety events: WHO Western Pacific regional experience and lessons learned.

Problem: Novel vaccines were developed in an unprecedentedly short time in response to the global coronavirus disease (COVID-19) pandemic, which triggered concerns about the safety profiles of the new vaccines. This paper describes the actions and outcomes of three major adverse events of special interest (AESIs) reported in the World Health Organization's (WHO's) Western Pacific Region: anaphylaxis, thrombosis with thrombocytopenia syndrome (TTS) and post-vaccination death. Context: During the large-scale introduction of various novel COVID-19 vaccines, robust monitoring of and response to COVID-19 vaccine safety events were critical. Action: We developed and disseminated information sheets about anaphylaxis and TTS; provided tailor-made training for anaphylaxis monitoring and response, webinars about TTS and AESIs, and an algorithm to support decision-making about AESIs following immunization; as well as provided country-specific technical support for causality assessments, including for possible vaccination-related deaths. Outcome: Each major vaccine event and situation of high concern was responded to appropriately and in a timely manner with comprehensive technical support from WHO. Our support activities have not only strengthened countries' capacities for vaccine safety surveillance and response, but also enabled countries to decrease the negative impact of these events on their immunization programmes and maintain the confidence of health-care professionals and the general population through proactive delivery of risk communications. Discussion: This paper summarizes selected, major AESIs following COVID-19 vaccination and responses made by WHO's Regional Office for the Western Pacific to support countries. The examples of responses to vaccine safety events during the pandemic and unprecedented mass vaccination campaigns could be useful for countries to adopt, where applicable, to enhance their preparation for activities related to monitoring vaccine safety.

COVID-19 vaccine-related adverse events following immunization in the WHO Western Pacific Region, 2021-2022.

The speed at which new vaccines against coronavirus disease (COVID-19) were developed and rolled out as part of the global response to the pandemic was unprecedented. This report summarizes COVID-19 vaccine-related safety data in the World Health Organization Western Pacific Region. Data for 1 March 2021 to 31 March 2022 from 36 out of 37 countries and areas in the Western Pacific Region are presented. More than 732 million doses of eight COVID-19 vaccines were administered; reporting rates of adverse events following immunization (AEFIs) and serious AEFIs were 130.1 and 5.6 per 100 000 doses administered, respectively. Anaphylaxis, thrombosis with thrombocytopenia syndrome, and myocarditis/pericarditis were the most frequent COVID-19 adverse events of special interest (AESIs) reported. The reported rates of AESIs in the Western Pacific Region were within the range of expected or background rates. Vaccine benefits far outweigh the risk of reported serious adverse reactions and serious outcomes of COVID-19. Continued AEFI surveillance is recommended to better understand and ensure the safety profiles of novel COVID-19 vaccines.

Long-term trajectory of postoperative health-related quality of life in young breast cancer patients: a 15-year follow-up study.

PURPOSE: Breast cancer (BC) patients often experience various long-term sequelae due to aggressive treatment. We analyzed and illustrated long-term trajectory during different phases of treatment and survivorship. METHODS: Data were obtained from a cohort of 298 BC patients diagnosed between 2004 and 2006 and were followed up until 2020. We measured HRQoL using EORTC QLQ-C30, QLQ-BR23, and EuroQoL-5D questionnaires and conducted eight assessments right after initial diagnosis, during treatment, post-treatment, and during survivorship phases. Linear mixed model was used to assess changes in HRQoL. Overall HRQoL measured by EQ-5D index of long-term BC survivors were further compared with that of the age-matched general population. RESULTS: Of 298 participants, 246 women survived and 124 participated in the long-term follow-up survey (LTFU). Overall, HRQoL functions deteriorated during treatment but gradually improved between 1- and 3-year post-diagnosis and stabilized over LTFU measure. Significant recovery was observed in physical, role, emotional, social functions, and future perspectives (p < 0.05). Treatment-related acute symptoms were reported in the first year but diminished afterward, and treatment-related financial difficulties lessened. At LTFU, BC survivors reported a high level of insomnia, fatigue, and pain and appeared to have poorer overall HRQoL than the general population (mean difference, EQ-5D index: 0.073, p < 0.001). CONCLUSIONS: Through 15-year survivorship, BC survivors showed improvement in many aspects of HRQoL. However, some inferior aspects remain relevant for long-term survivors. Ongoing supportive programs concentrating on pain management, persistent cancer-related fatigue, and sleeping problems might aid enhance their HRQoL.

Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea.

PURPOSE: This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women. METHODS: The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16 years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates. RESULTS: Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001). CONCLUSION: Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL. IMPLICATIONS FOR CANCER SURVIVORS: This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

Multiplicative synergistic risk of hepatocellular carcinoma development among hepatitis B and C co-infected subjects in HBV endemic area: a community-based cohort study.

BACKGROUND: There has been limited study on the effect of infection with different hepatitis C virus (HCV) genotypes on the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) endemic regions of Asia. METHODS: Hazard ratios of HCC development were estimated for HBV and HCV co-infected subjects among a community-based prospective cohort. HCV genotype was determined in HCV RNA-positive samples. Incident HCC cases were identified through linkage to the cancer registry. RESULTS: HCC incidence was 79 per 100,000 person-years in the study population (50 incident cases among 6,694 individuals within 63,170 person-years with an average of 9.4 years of follow-up); seroprevalence of HBsAg and anti-HCV was 5.2% and 5.6%. Adjusted hazard ratios of HCC by HBsAg positivity and anti-HCV positivity were 13.3 (CI: 7.3-24.4) and 6.7 (CI: 3.6-12.6). HRs of HBV and HCV monoinfection, and HBV/HCV coinfection were 17.1 (CI: 8.4-34.8), 10.4 (CI: 4.9-22.1) and 115.0 (CI: 32.5-407.3). Multiplicative synergistic effect of HBV/HCV coinfection on HCC risk was also observed (synergy index: 4.5, CI: 1.3-15.5). Infection with HCV genotype 1 (HR: 29.7, CI: 13.6-46.8) and mixed infection with genotype 1 and 2 (HR: 68.7, CI: 16.4-288.4) significantly elevated HCC risk, much higher than HBV infection. CONCLUSIONS: The effect of differences in HCV genotype and the multiplicative synergistic effect of HBV/HCV coinfection on HCC risk shown in the present study underline the need for comprehensive identification of hepatitis infection status in order to prevent and control HCC in this HBV endemic area.

Fear of Cancer Recurrence and Its Negative Impact on Health-Related Quality of Life in Long-term Breast Cancer Survivors.

PURPOSE: Fear of cancer recurrence (FCR) is a common psychological issue in breast cancer (BC) survivors during early survivorship but whether the same is true among long-term survivors has yet to be empirically evaluated. This study investigated FCR level, its associated factors, and impact on quality of life (QoL) in long-term BC survivors. MATERIALS AND METHODS: Participants included women diagnosed with BC between 2004 and 2010 at two tertiary hospitals. Survey was conducted in 2020. The study measured FCR with the Fear of Cancer Recurrence Inventory and other patient-reported outcomes, including depression and cancer-related QoL. Logistic regression was used to identify factors associated with FCR, and structural equation modeling was conducted to explore the impact of FCR on other outcomes. RESULTS: Of 333 participants, the mean age at diagnosis was 45.5, and 46% experienced FCR. Age at diagnosis ≤ 45 (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.51 to 4.60), shorter time since diagnosis (aOR, 1.75, 95% CI, 1.08 to 2.89), and having a history of recurrence (aOR, 2.56; 95% CI, 1.16 to 5.65) was associated with more FCR. FCR was significantly associated with an increased risk of depression (ß=0.471, p < 0.001) and negatively impacted emotional functioning (ß=-0.531, p < 0.001). In addition, a higher FCR level may impair overall health-related QoL in long-term BC survivors (ß=-0.108, p=0.021). CONCLUSION: Ten years after diagnosis, long-term BC survivors still experienced a high level of FCR. Further, the negative impact of FCR on QoL and increased depression risk require an FCR screening and appropriate interventions to enhance long-term BC survivors' QoL.

Associations of physical activity at work and household income with obesity: a cross-sectional study among rural adults in Korea.

OBJECTIVES: This study was performed to identify the effect of physical activity at work on obesity and to analyze the contribution of socioeconomic factors and health behaviors to this association, which has been relatively little studied. METHODS: From the Korean National Cancer Center Community Cohort, a total of 5,587 adults (2,125 men; 3,462 women) aged more than 30 years living in rural areas were enrolled. Information on socio-demographic factors, health behaviors, and body mass index was gathered using face-to-face interviews and measurements of height and weight. RESULTS: Inverse associations were identified between vigorous-intensity physical activity at work and obesity in both men and women, while no association was found between vigorous-intensity physical activity during leisure time and obesity. High household income was independently associated with a lower risk of obesity among those who had low levels of vigorous-intensity physical activity at work. Vigorous physical activity at work showed an inverse association with obesity in rural areas where heavy manual labor is common. CONCLUSIONS: Our findings indicate the necessity to account for various types of physical activity to improve the assessment and prevention of obesity.

Economic burden of alcohol-related cancers in the Republic of Korea.

BACKGROUND: Cancer is a major burden of disease and alcohol consumption is one of the major risk factors of cancer. This study aimed to estimate the economic burden of cancer types attributable to alcohol consumption in the Republic of Korea. METHODS: This study estimates the direct and indirect costs of cancer types attributable to alcohol consumption by applying cost-of-illness methods using the human capital approach and prevalence-based estimates. Claims data from the National Health Insurance Service for 2011-2016 were used. RESULTS: In Korea, there were 297,304 alcohol consumption-related cancer cases, of which 14,186 (4.8 %) were attributable to alcohol consumption in 2016. From 2011-2016, the socioeconomic burden of cancer attributable to alcohol consumption in Korea has increased steadily, even considering inflation adjustment. The total economic burden of cancer attributable to alcohol consumption in 2016 in Korea was approximately $476 million, of which $119 million were direct costs and $357 million were indirect costs. According to our analysis of annual cost per patient, the average costs were $37,432 for men and $11,930 for women. CONCLUSIONS: The economic burden of cancer types attributable to alcohol consumption in Korea is substantial and has increased between 2011 and 2016, mainly due to an increased number of patients.

The Effects of Music Therapy-Singing Group on Quality of Life and Affect of Persons With Dementia: A Randomized Controlled Trial.

Dementia is a clinical syndrome that is progressive and degenerative, affecting memory, behavior, emotion, and personality. Persons with dementia often experience deterioration of cognitive ability, as well as various behavioral and psychological disturbances, which significantly contribute to reduced quality of life and emotional well-being. The demand for long-term care continues to rise rapidly and it is therefore critical to develop effective strategies and evidence-based interventions to improve the quality of life for persons with dementia. Music therapy has drawn attention as a promising non-pharmacological approach for persons with dementia. A variety of music interventions including singing and listening to music have been widely applied for dementia care not only by music therapists, but also by other healthcare professionals. There are, however, little research studies that compare possible effects of music therapy interventions with those of music-based approaches on dementia care. The purpose of the current study was to compare the short-term effects of a music therapy-singing group with those of a music medicine-listening group and a control-TV group, on quality of life and affect of persons with dementia at a long-term care facility. The music therapy-singing group was facilitated by a music therapist, whereas the music medicine-listening and the control-TV group were led by nursing home activity staff. Fifty-two participants, whose ages range from 67 to 99 years old, were randomly assigned to one of the three groups, and 37 participants completed the interventions. The participants in each group were engaged for a 40-min session twice a week for four consecutive weeks. Quality of life was measured at the baseline and after the last session and only the music therapy-singing group demonstrated significant improvements when compared to the other groups. Positive and negative affect were measured at three points, including pre and post the first, fourth and eighth sessions. Only the music therapy-singing group significantly increased positive affect scores and decreased negative affect scores. The findings of the current study suggest that music therapy with active group singing may be an effective non-pharmacological intervention in improving quality of life and affect of persons with dementia at long-term care settings. Clinical Trial Registration: http://www.germanctr.de/drks_web/, registration number DRKS00014934.

Development of Middle East Respiratory Syndrome Coronavirus vaccines - advances and challenges.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging pathogen with the potential to pose a threat to global public health. Sporadic cases and outbreaks continue to be reported in the Middle East, and case fatality rates remain high at approximately 36% globally. No specific preventive or therapeutic countermeasures currently exist. A safe and effective vaccine could play an important role in protecting against the threat from MERS-CoV. This review discusses human vaccine candidates currently under development, and explores viral characteristics, molecular epidemiology and immunology relevant to MERS-CoV vaccine development. At present, a DNA vaccine candidate has begun a human clinical trial, while two vector-based candidates will very soon begin human trials. Protein-based vaccines are still at pre-clinical stage. Challenges to successful development include incomplete understanding of viral transmission, pathogenesis and immune response (in particular at the mucosal level), no optimal animal challenge models, lack of standardized immunological assays, and insufficient sustainable funding.

Thrombus and Plaque Erosion Characterized by Optical Coherence Tomography in Patients With Vasospastic Angina.

INTRODUCTION AND OBJECTIVES: Vasospastic angina (VSA) can result in endothelial damage and thrombus formation. The aim of this study was to evaluate the incidence of thrombus and plaque characteristics at coronary spasm segments compared with nonspasm segments by using optical coherence tomography (OCT) in patients with suspected VSA. METHODS: One hundred and eighty-three patients with suspected VSA were enrolled in this study. The ergonovine provocation test was performed in all patients for the diagnosis of VSA except in patients with spontaneous spasm. All target lesions were analyzed by OCT. Plaque erosion was defined as the presence of attached thrombus overlying an intact fibrous cap and visualized plaque on multiple adjacent OCT frames. RESULTS: One hundred and nine spasm segments (93 patients) were compared with 55 nonspasm segments (39 patients). Thrombus was more frequently seen at spasm segments than at nonspasm segments (28.4% vs 7.3%; P = .026) and thrombus size was larger at spasm segments than at nonspasm segments (0.26 ± 0.50 mm2 vs 0.04 ± 0.01 mm2; P = .023). Thin-cap fibroatheroma was more frequently seen at nonspasm segments than at spasm segments (16.4% vs 1.8%; P = .006). Plaque erosion was more prevalent at spasm segments than at nonspasm segments (25.7% vs 5.4%; P = .001). CONCLUSIONS: Thrombus and plaque erosion were more common at spasm segments than at nonspasm segments assessed by OCT in patients with suspected VSA. These findings suggest the potential benefit and treatment role of antiplatelet therapy in vasospastic angina.

Plaque Characteristics and Ruptured Plaque Location according to Lesion Geometry in Culprit Lesions of ST-Segment Elevation Myocardial Infarction.

BACKGROUND AND OBJECTIVES: The correlations between plaque characteristics and plaque rupture location according to segmental lesion analysis have not been well defined. The aim of this study was to assess those characteristics of ST-segment elevation myocardial infarction (STEMI) culprit lesions according to segmental lesion geometry using virtual histology intravascular ultrasound (VH-IVUS). METHODS: Sixty single discrete lesions found in the left anterior descending (LAD) coronary arteries of 60 patients with STEMI were included. Each lesion was divided into 3 segments based on lumen area (LA) index, calculated by dividing the lesion LA by the reference LA. RESULTS: Among the 3 segments, the mid-segment showed the highest proportion of necrotic core (NC; proximal, mid-, and distal segments: 20.9±11.8%, 22.7±11.3%, and 17.5±11.2%, respectively, p=0.044). VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) was also more frequently found in the mid-segment than in proximal and distal segments (36.7%, 58.3%, and 16.7%, p<0.001). The mid-segment also showed the highest prevalence of plaque rupture (45.0%, 78.3% and 11.7%, p<0.001) and thrombus (61.7%, 95.0%, and 41.7%, p<0.001) compared to proximal or distal segments. When the lesions were divided into 2 groups according to the median value (4.0 mm²) of minimum lumen area (MLA), plaque rupture at the distal segment was observed only in high MLA lesions (23.3% vs. 0.0%, p=0.011). CONCLUSION: Analysis of longitudinal lesion geometry using the LA index can be useful in evaluating plaque vulnerability and the incidence of plaque rupture and thrombus in STEMI patients.

Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels.

We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day) and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI): AST, 2.37 [1.20-4.67]; GGT, 1.91 [1.17-3.13]). Only GGT level (odds ratio 6.04 [3.68-9.94], SI 2.33 [1.24-4.41]) was significantly elevated when the effect of moderate drinking (<24 g/day) and metabolic syndrome was combined. The combined effect of any level of alcohol consumption and cigarette smoking was also supra-additive on the elevation of GGT level with SIs of 5.57 for drinking <24 g/day and smoking ≤20 pack years, 5.12 for <24 g/day and >20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12-6.61]). The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

Association of vascular endothelial growth factor polymorphisms with nonproliferative and proliferative diabetic retinopathy.

CONTEXT: Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor, and its polymorphisms are associated with proliferative diabetic retinopathy (PDR) and macular edema. OBJECTIVE: We investigated the contributions of VEGF gene polymorphisms to nonproliferative diabetic retinopathy (NPDR) as well as PDR. DESIGN, SETTING, AND SUBJECTS: In this study we compared VEGF gene variants in a sample of Korean type 2 diabetes patients with and without diabetic retinopathy (DR) and in healthy controls. Of the diabetes patients, 145 had PDR, 108 had NPDR, and 134 had no retinopathy (noDR). They were all duration matched. Samples were genotyped for rs699947, rs1570360, and rs2010963 polymorphisms. RESULTS: We found a significant association between the A allele at rs699947 with DR (odds ratio = 1.84 (95% confidence interval = 1.28-2.66); P = 0.001 vs. noDR). Patients with NPDR, as well as PDR, had increased incidence of the A allele. The AGG haplotype was more frequently found in patients with DR than in patients with noDR (odds ratio = 4.79 (95% confidence interval = 1.42-16.16); P = 0.006). PDR and NPDR patients exhibited an increased incidence of the AGG haplotype. CONCLUSIONS: VEGF polymorphisms might be a useful predictive marker for the development and progression of DR at an earlier stage of diabetes.

Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.

Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-gene interaction using logistic regression analysis. Associations between 13 genes and longevity were detected at a P-value less than 0.01. Particularly, the rs671 (A) allele of the aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) gene was associated with longevity only in men (OR 2.11, P =0.008). Four genes, proprotein convertase subtilisin/kexin type 1 (PCSK1, P=0.008), epidermal growth factor receptor (EGFR, P=0.003), paired box 4 (PAX4, P=0.008), and V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN, P=0.002) consistently yielded statistical evidence for association with longevity. The findings of the current study may provide a starting point for future studies to unravel genetic factors controlling longevity in Koreans.