Polycystic ovary syndrome (PCOS) is a heterogenous endocrine disorder with typical symptoms of oligomenorrhoea, hyperandrogenism, hirsutism, obesity, insulin resistance and increased risk of type 2 diabetes mellitus. Extensive evidence indicates that PCOS is a genetic disease and numerous biochemical pathways have been linked with its pathogenesis. A number of genes from these pathways have been investigated, which include those involved with steroid hormone biosynthesis and metabolism, action of gonadotropin and gonadal hormones, folliculogenesis, obesity and energy regulation, insulin secretion and action and many others. In this review, we summarize the historical and recent findings in genetic polymorphisms of PCOS from the relevant publications and outline some genetic polymorphisms that are potentially associated with the risk of PCOS. This information could uncover candidate genes associating with PCOS, which will be valuable for the development of novel diagnostic and treatment platforms for PCOS patients.
Yao Chen and Shu-ying Fang
Zhen-yu Song, Qiuming Yao, Zhiyuan Zhuo, Zhe Ma and Gang Chen
Previous studies investigating the association of circulating 25-hydroxyvitamin D level with prognosis of prostate cancer yielded controversial results. We conducted a dose–response meta-analysis to elucidate the relationship. PubMed and EMBASE were searched for eligible studies up to July 15, 2018. We performed a dose–response meta-analysis using random-effect model to calculate the summary hazard ratio (HR) and 95% CI of mortality in patients with prostate cancer. Seven eligible cohort studies with 7808 participants were included. The results indicated that higher vitamin D level could reduce the risk of death among prostate cancer patients. The summary HR of prostate cancer-specific mortality correlated with an increment of every 20 nmol/L in circulating vitamin D level was 0.91, with 95% CI 0.87–0.97, P = 0.002. The HR for all-cause mortality with the increase of 20 nmol/L vitamin D was 0.91 (95% CI: 0.84–0.98, P = 0.01). Sensitivity analysis suggested the pooled HRs were stable and not obviously changed by any single study. No evidence of publications bias was observed. This meta-analysis suggested that higher 25-hydroxyvitamin D level was associated with a reduction of mortality in prostate cancer patients and vitamin D is an important protective factor in the progression and prognosis of prostate cancer.
Ning Yao, Chunbei Zhou, Jun Xie, Xinshu Li, Qianru Zhou, Jing Chen and Shuang Zhou
The remarkable success of iodine deficiency disorders (IDD) elimination in China has been achieved through a mandatory universal salt iodization (USI) program. The study aims to estimate the relationship between urinary iodine concentration (UIC) and iodine content in edible salt to assess the current iodine nutritional status of school aged children.
A total of 5565 students from 26 of 39 districts/counties in Chongqing participated in the study, UIC and iodine content in table salt were measured. Thyroid volumes of 3311 students were examined by ultrasound and goiter prevalence was calculated.
The overall median UIC of students was 222 μg/L (IQR: 150-313 μg/L). Median UIC was significantly different among groups with non-iodized salt (iodine content <5 mg/kg), inadequately iodized salt (between 5 and 21 mg/kg), adequately iodized (between 21 and 39 mg/kg) and excessively iodized (>39 mg/kg) salt (P < 0.01). The total goiter rate was 1.9% (60/3111) and 6.0% (186/3111) according to Chinese national and WHO reference values, respectively. Thyroid volume and goiter prevalence were not different within the three iodine nutritional status groups (insufficient, adequate and excessive, P > 0.05).
The efficient implementation of current USI program is able to reduce the goiter prevalence in Chongqing as a low incidence of goiter in school aged children is observed in this study. The widened UIC range of 100–299 μg/L indicating sufficient iodine intake is considered safe with a slim chance of causing goiter or thyroid dysfunction. Further researches were needed to evaluate the applicability of WHO reference in goiter diagnose in Chongqing or identifying more accurate criteria of normal thyroid volume of local students in the future.
Qiuli Liu, Gang Yuan, Dali Tong, Gaolei Liu, Yuting Yi, Jun Zhang, Yao Zhang, Lin-ang Wang, Luofu Wang, Dianzheng Zhang, Rongrong Chen, Yanfang Guan, Xin Yi, Weihua Lan and Jun Jiang
Von Hippel–Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype–phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes.
Patients and design
A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients’ gene sequencing results with their medical records including CT or MRI scans, eye examinations and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history.
We identified four missense mutations: c.239G>T (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma, pheochromocytoma and hemangioma in the cerebellum; c.232A>T (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G>A (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum and spinal cord; c.293A>G (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2.
Characterizing VHL disease genotype–phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance and treatment of VHL patients.
Four missense mutations in VHL have been identified in 21 individuals when five unrelated Chinese families with VHL disease were analyzed; VHL mutations are highly associated with unique disease phenotypes.
Yiqiang Huang, Lin-ang Wang, Qiubo Xie, Jian Pang, Luofu Wang, Yuting Yi, Jun Zhang, Yao Zhang, Rongrong Chen, Weihua Lan, Dianzheng Zhang and Jun Jiang
Pheochromocytoma and paragangliomas (PCC/PGL) are neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and sympathetic/parasympathetic ganglia, respectively. Of clinical relevance regarding diagnosis is the highly variable presentation of symptoms in PCC/PGL patients. To date, the clear-cut correlations between the genotypes and phenotypes of PCC/PGL have not been entirely established. In this study, we reviewed the medical records of PCC/PGL patients with pertinent clinical, laboratory and genetic information. Next-generation sequencing (NGS) performed on patient samples revealed specific germline mutations in the SDHB (succinate dehydrogenase complex iron-sulfur subunit B) and SDHD (succinate dehydrogenase complex subunit D) genes and these mutations were validated by Sanger sequencing. Of the 119 patients, two were identified with SDHB mutation and one with SDHD mutation. Immunohistochemical (IHC) staining was used to analyze the expression of these mutated genes. The germline mutations identified in the SDH genes were c343C>T and c.541-542A>G in the SDHB gene and c.334-337delACTG in the SDHD gene. IHC staining of tumors from the c.343C>T and c.541-2A>G carriers showed positive expression of SDHB. Tumors from the c.334-337delACTG carrier showed no expression of SDHD and a weak diffused staining pattern for SDHB. We strongly recommend genetic testing for suspected PCC/PGL patients with a positive family history, early onset of age, erratic hypertension, recurrence or multiple tumor sites and loss of SDHB and/or SDHD expression. Tailored personal management should be conducted once a patient is confirmed as an SDHB and/or SDHD mutation carrier or diagnosed with PCC/PGL.