FTO variants are associated with obesity in the Chinese and Malay populations in Singapore

OBJECTIVE— Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations.RESEARCH DESIGN AND METHODS— We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES).RESULTS— All nine SNPs exhibited strong linkage disequilibrium (r² = 0.6–0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m² (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m² (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m² (P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17–1.22; P ≤ 0.026).CONCLUSIONS— FTO variants common among European populations are associated with obesity in ethnic Chinese and Malays in Singapore. Our data do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes.A recent genome-wide association study for type 2 diabetes using a U.K.-based population revealed a novel locus associated with BMI: the fat mass–and obesity-related gene (FTO) on chromosome 16 (1). The representative single-nucleotide polymorphism (SNP), rs9939609, was confirmed to be associated with elevated BMI after replication in more than 38,000 study participants of European ancestry. Further replication of this association has been observed in several populations of distinctly European ancestry (2–6). However, this association is inconsistent in populations of non-European ancestry. A study in Japanese showed an association between variants at this locus and obesity (7) that was not observed in African Americans (6) or Han Chinese (8). The aims of this study were 1) to determine the associations between previously identified obesity-associated SNPs at the FTO locus with obesity and type 2 diabetes in Chinese, Malays, and Asian-Indians and 2) to examine whether any associations were modulated by exercise.     

Urinary tract infections following renal transplantation: a single-center experience

BACKGROUND: Although infectious complications are the second most common cause of death after transplantation, there appears to be insufficient data regarding the impact of urinary tract infections (UTIs) on graft outcome and patient mortality and morbidity. In this study, we evaluated the incidence, risk factors, and long-term effects of UTIs on graft function. METHOD: We performed a retrospective cohort study reviewing the medical records of patients who received a renal transplant at our center from January 1999 to December 2006. All UTIs, risk factors, long-term graft function, graft loss, and death were recorded. Outcomes among patients with UTIs were compared with those without UTIs. RESULTS: Fifty-six of 136 patients (41.2%) had at least one UTI over a mean period of 38+/-25 months after transplantation. While there was a tendency toward graft loss among patients with UTIs (16.1% vs 6.3%, P=.08), there was no increased risk of death. The patients with UTIs displayed higher serum creatinine levels (1.7+/-1.4 vs 2.3+/-2.5 mg/dL, P=.07) compared to non-UTI patients in the long term. Upon multivariate analysis, female gender was the only risk factor for posttransplant UTIs. We did not determine any immunosuppressive drug as a risk factor for UTIs. The most frequent pathogens isolated in urine culture were Escherichia coli (n=72, 59.1%) and Klebsiella spp (n=21, 16.9%), and there were eight cases of bacteremia. CONCLUSION: UTIs are a frequent problem after kidney transplantation. Female recipients are at greatest risk. In the long-term, UTIs should be considered as a potential risk for poorer graft outcomes.     

Non-cytotoxic and sublethal paclitaxel treatment potentiates the sensitivity of cultured ovarian tumor SKOV-3 cells to lysis by lymphokine-activated killer cells

BACKGROUND: The standard treatment of epithelial ovarian cancer is tumor debulking by surgery, followed by six cycles of chemotherapy consisting of cisplatinum and paclitaxel. However, this therapy protocol is not satisfactory, since about 50% of the treated patients eventually experience recurrence within a few years of follow-up. Thus, a more innovative treatment modality is urgently needed for patients with this malignancy. We hypothesized that pretreatment of ovarian cancer SKOV-3 cells at a non-cytotoxic to sublethal dose range of paclitaxel would result in increased sensitivity to LAK-mediated killing. MATERIALS AND METHODS: MTT and trypan blue dye exclusion were used to determine the non-cytotoxic to sublethal range of paclitaxel against SKOV-3 cells. A 4-h 51Cr release cytotoxicity assay was used to evaluate the sensitivity of paclitaxel-treated and untreated SKOV-3 cells. Immunofluorescence/flow cytometric analysis was used for phenotypic changes of cells with or without paclitaxel treatment. RESULTS: Our results with trypan blue dye exclusion and MTT assays showed that the non-cytotoxic to sublethal range was between 0.001 microM and 0.01 microM. Pretreatment of SKOV-3 cells with paclitaxel at these doses for 72 h revealed significantly enhanced LAK-mediated killing against SKOV-3 cells with the highest sensitivity achieved with cells treated with 0.001 microM paclitaxel, as compared with the baseline killing of untreated cells using LAK cell alone (p < 0.05). The enhanced sensitivity of LAK-mediated killing appeared to be in part due to paclitaxel-induced expression of ICAM-1 on SKOV-3 cells. CONCLUSION: This treatment approach may be useful for further development of an effective therapeutic mode for patients with ovarian cancer.     

Measuring Fear of Childbirth Among a Diverse Population in the United States: A Revised Wijma Delivery Expectancy/Experience Scale (WDEQ-10)

Introduction

The current gold standard instrument used to measure fear of childbirth is the Wijma Delivery Expectancy/Experience Questionnaire (WDEQ). However, the existing scale is long, has translational challenges, and lacks data specific to experiences of a diverse population in the United States, making it challenging to assess how fear of childbirth impacts perinatal health care disparities. The objective of this study was to revise the WDEQ and analyze its reliability and validity for use in the United States.

Methods

The questionnaire was revised using qualitative data from a previously published study of fear of childbirth within a racially, ethnically, and economically diverse group of pregnant or postpartum people in the United States. Psychometric properties were analyzed in terms of construct validity, reliability, and factor analysis from a group of 329 participants.

Results

The revised and shortened 10 item WDEQ-10 comprises 3 subscales: fear of environmental factors, fear of death or injury, and fear of how they feel. The results indicate that the WDEQ-10 demonstrates good reliability and validity and confirmed the multidimensionality of fear of childbirth through a 3-factor solution.

Discussion

The WDEQ-10 is a readable and accessible instrument that will allow health care providers and researchers to accurately measure complex components of how pregnant people experience fear of childbirth.