Lin X.,Fudan Institute of Urology |
Lin X.,Fudan Center for Genetic Epidemiology |
Lu D.,Fudan University |
Gao Y.,Fudan Center for Genetic Epidemiology |
And 24 more authors.
Human Molecular Genetics | Year: 2012
Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 × 10-8. These four loci were MS4A3 (11q12.1; rs2298585; P= 2.64 × 10-15), CLYBL (13q32; rs41281112; P= 9.23 × 10-10), FUT6 (19p13.3; rs3760776; P= 3.68 × 10-13) and 5q32 region (rs10515552; P= 3.94 × 10-8). In addition, we also confirmed the association with the serum level of VitB12 for the previously reported FUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P= 3.62 × 10-36). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease. © The Author 2012. Published by Oxford University Press. All rights reserved.
Zhao H.,Shandong University |
Xu J.,Fudan University |
Xu J.,Fudan Institute of Urology |
Xu J.,Wake forest University |
And 32 more authors.
American Journal of Human Genetics | Year: 2012
A genome-wide association study of Han Chinese subjects was conducted to identify genetic susceptibility loci for nonobstructive azoospermia (NOA). In the discovery stage, 802 azoospermia cases and 1,863 controls were screened for genetic variants in the genome. Promising SNPs were subsequently confirmed in two independent sets of subjects: 818 azoospermia cases and 1,755 controls from northern China, and 606 azoospermia cases and 958 controls from central and southern China. We detected variants at human leukocyte antigen (HLA) regions that were independently associated with NOA (HLA-DRA, rs3129878, p combine = 3.70 × 10-16, odds ratio [OR] = 1.37; C6orf10 and BTNL2, rs498422, pcombine = 2.43 × 10 -12, OR = 1.42). These findings provide additional insight into the pathogenesis of NOA. © 2012 by The American Society of Human Genetics. All rights reserved.
Wang M.,Nanjing Medical UniversityNanjing China |
Du M.,Cancer Center |
Ma L.,Cancer Center |
Chu H.,Cancer Center |
And 8 more authors.
International Journal of Cancer | Year: 2016
The first genome-wide association study (GWAS) for bladder cancer has identified a susceptibility locus at 3q28 in the European ancestry. However, the causal variant at 3q28 remains unknown. We conducted a three-stage fine mapping study to identify potential causal variants in the region. A total of 41 single nucleotide polymorphisms (SNPs) across 120 kb at 3q28 were tested for association with bladder cancer risk among 3,094 bladder cancer cases and 3,738 controls. Resequencing and functional assays were further evaluated. The SNP rs35592567 in the 3'-UTR of TP63 was consistently associated with bladder cancer risk in all three stages. In the combined analysis, the T allele of rs35592567 was significantly associated with a decreased risk for bladder cancer (OR=0.82, 95% CI=0.75-0.90, P=9.797 × 10-6 in the additive model). Biochemical assays revealed that the T allele reduced the post-transcriptional levels of TP63 mediated by interfering binding efficiency of miR-140-5p. In addition, overexpression of miR-140-5p inhibited bladder cancer cell proliferation and attenuated cell migration, invasion and G1 cell-cycle arrest. Together, these results suggest that rs35592567 in TP63 may be a novel causal variant contributing to the susceptibility to bladder cancer, which provides additional insight into the pathogenesis of bladder carcinogenesis. © 2015 UICC.
Hu Q.,Huashan Hospital |
Hu Q.,Fudan Institute of Urology |
Hu Q.,Fudan University |
Hang Z.,Fudan University |
And 16 more authors.
Urologia Internationalis | Year: 2015
Introduction: Obesity is usually considered a risk factor for postoperative complications; however, previous studies conclude contradictory results in retroperitoneal laparoscopic adrenalectomy (LA). We aim to evaluate the impact of obesity on the perioperative outcomes of LA. Methods: A retrospective cohort study from a single center including 353 patients from 2011 to 2013 was conducted. Perioperative outcomes of patients from different groups were compared according to their body mass index (BMI). Results: All the patients were divided into 3 groups: normal (n = 149), overweight (n = 141) and obese (n = 63). Operative time (OT) for patients belonging to the obese group was significantly longer than that in the normal and overweight group, and the results of estimated blood loss, postoperative length of stay in hospital and postoperative complications were all similar. In the multivariate logistic regression analysis, OT was an independent risk factor for postoperative complications (odds ratio 1.020; 95% confidence interval 1.001-1.039; p = 0.037), while other factors including BMI had negligible effect. Conclusions: Retroperitoneal LA offers similar perioperative outcomes for patients with different obesity statuses, which could be safe and feasible for obese patients. © 2015 S. Karger AG, Basel.