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Genetic Variants in Six-Transmembrane Epithelial Antigen of Prostate 4 Increase Risk of Developing Metabolic Syndrome in a Han Chinese Population.

ABSTRACT: Altered expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) is linked to obesity, insulin insensitivity, metabolic homeostasis, and inflammation. This study assessed STEAP4 single nucleotide polymorphisms (SNPs) for association with a risk in developing metabolic syndrome in a Han Chinese population.A total of 3375 Han Chinese subjects were included in this case-control study with 1583 metabolic syndrome (MetS) patients and 1792 healthy controls. Four SNPs (rs1981529, rs2040657, rs10263111, rs12386756) were genotyped using polymerase chain reaction and MALDI-TOF-MS. The associations between the STAMP4 SNPs and MetS were then analyzed statistically.There was no statistical difference in allele frequency of these four SNPs between the case and control populations. The genotype of rs12386756 was shown to be significantly associated with MetS (p?=?0.035). Compared with the AA/GG genotypes, the GA genotype of rs12386756 significantly decreased the risk of developing MetS (OR?=?0.77; 95% CI, 0.63-0.94; p?=?0.0098). There was also no haplotype that could be associated with the risk of developing MetS. Furthermore, the SNP rs1981529 of STEAP4 was associated with body-mass index, waist circumference, and systolic blood pressure, while SNP rs10263111 was associated with waist circumference and fasting glucose levels. SNP rs12386756 was associated with waist and hip circumferences.Some SNPs of the STEAP4 gene altered the risk of developing a metabolic syndrome in the Han Chinese population. Further studies must be conducted to understand the role of the STEAP4 gene in the pathogenesis of metabolic syndrome.

SUBMITTER: Qi Y

PROVIDER: S-EPMC4677533 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Genetic Variants in Six-Transmembrane Epithelial Antigen of Prostate 4 Increase Risk of Developing Metabolic Syndrome in a Han Chinese Population.

Qi Yue Y Yu Yaqin Y Wu Yanhua Y Wang Shibin S Yu Qiong Q Shi Jieping J Xu Ziqi Z Zhang Qingqing Q Fu Yingli Y Fu Yao Y Kou Changgui C

Genetic testing and molecular biomarkers 20151028 12

<h4>Background</h4>Altered expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) is linked to obesity, insulin insensitivity, metabolic homeostasis, and inflammation. This study assessed STEAP4 single nucleotide polymorphisms (SNPs) for association with a risk in developing metabolic syndrome in a Han Chinese population.<h4>Methods</h4>A total of 3375 Han Chinese subjects were included in this case-control study with 1583 metabolic syndrome (MetS) patients and 1792 healthy co ...[more]

PMID: 26510124

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Project description:PURPOSE:Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is highly expressed in prostate cancers. DSTP3086S is a humanized immunoglobulin G1 anti-STEAP1 monoclonal antibody linked to the potent antimitotic agent monomethyl auristatin E. This study evaluated the safety and activity of DSTP3086S in patients with metastatic castration-resistant prostate cancer. METHODS:Patients were enrolled in a 3 + 3 dose escalation study to evaluate DSTP3086S (0.3 to 2.8 mg/kg intravenously) given once every 3 weeks followed by cohort expansion at the recommended phase II dose or weekly (0.8 to 1.0 mg/kg). RESULTS:Seventy-seven patients were given DSTP3086S once every 3 weeks, and seven were treated weekly. Two patients in the once-every-3-weeks dose escalation had dose-limiting grade 3 transaminitis. Grade 3 hyperglycemia and grade 4 hypophosphatemia were dose-limiting toxicities in one patient treated at 1.0 mg/kg weekly. Initial cohort expansion evaluated dosing at 2.8 mg/kg once every 3 weeks (n = 10), but frequent dose reductions led to testing of 2.4 mg/kg (n = 39) in the expansion phase. Common related adverse events (> 20%) across doses (once every 3 weeks) were fatigue, peripheral neuropathy, nausea, constipation, anorexia, diarrhea, and vomiting. DSTP3086S pharmacokinetics were linear. Among 62 patients who received > 2 mg/kg DSTP3086S once every 3 weeks, 11 (18%) demonstrated a ≥ 50% decline in prostate-specific antigen; two (6%) of 36 with measurable disease at baseline achieved a radiographic partial response; and of 27 patients with informative unfavorable baseline circulating tumor cells ≥ 5/7.5 mL of blood, 16 (59%) showed conversions to favorable circulating tumor cells < 5. No prostate-specific antigen or RECIST responses were seen with weekly dosing. CONCLUSION:DSTP3086S has acceptable safety at the recommended phase II dose level of 2.4 mg/kg once every 3 weeks. Antitumor activity at doses between 2.25 and 2.8 mg/kg once every 3 weeks supports the potential benefit of treating STEAP1-expressing metastatic castration-resistant prostate cancer with an STEAP1-targeting antibody-drug conjugate.

Dataset Information

Genetic Variants in Six-Transmembrane Epithelial Antigen of Prostate 4 Increase Risk of Developing Metabolic Syndrome in a Han Chinese Population.

Publications

Genetic Variants in Six-Transmembrane Epithelial Antigen of Prostate 4 Increase Risk of Developing Metabolic Syndrome in a Han Chinese Population.

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