Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed.

Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations.

Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.

Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.

An independent positive relationship between the serum total osteocalcin level and fat-free mass in healthy premenopausal women.

Context: It is widely reported that osteocalcin is negatively associated with fat mass. However, there are few reports describing its correlation with fat-free mass, particularly in women.

Objectives: The objective of the current study was to investigate the possible relationship between osteocalcin and fat-free mass in healthy, nonobese women.

A refined study of FCRL genes from a genome-wide association study for Graves' disease.

To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.

The effects of bisphenol A (BPA) exposure on fat mass and serum leptin concentrations have no impact on bone mineral densities in non-obese premenopausal women.

Objectives: Bisphenol A (BPA) exposure may promote obesity, but its effect on bone mineral density (BMD) has not been reported in humans. We aimed to examine the relationships between BPA exposure, body composition, serum estradiol, leptin, osteocalcin levels and BMDs in healthy premenopausal women.

Design And Methods: In this cross-sectional study, a total of 246 healthy premenopausal women aged 20 years and older with regular menstrual cycles were investigated.

A genome-wide association study identifies two new risk loci for Graves' disease.

Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls.

Two unusual cases of intractable hyperthyroidism responsive to octreotide: Munchausen syndrome or not?

Background: The effective treatment for patients with resistant hyperthyroidism is difficult.

Methods: In this case report with 4-year follow-up data, we present 2 unusual cases of hyperthyroidism that were unresponsive to almost all antithyroid treatments including total thyroidectomy, but both were controlled with octreotide.

Results: Cases 1 and 2 were both middle-aged women.

Association of the CTLA4 gene with Graves' disease in the Chinese Han population.

To determine whether genetic heterogeneity exists in patients with Graves' disease (GD), the cytotoxic T-lymphocyte associated 4 (CTLA-4) gene, which is implicated a susceptibility gene for GD by considerable genetic and immunological evidence, was used for association analysis in a Chinese Han cohort recruited from various geographic regions. Our association study for the SNPs in the CTLA4 gene in 2640 GD patients and 2204 control subjects confirmed that CTLA4 is the susceptibility gene for GD in the Chinese Han population. Moreover, the logistic regression analysis in the combined Chinese Han cohort revealed that SNP rs231779 (allele frequencies p = 2.

A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism.

Leydig cell hypoplasia (LCH) is a rare form of male pseudohermaphroditism caused by inactivating mutations in the luteinizing hormone receptor gene (LHCGR). The majority of LHCGR mutations are located in the coding sequence, resulting in impairment of either LH/CG binding or signal transduction. We report a Chinese family with two siblings (46, XY and 46, XX) carrying a missense mutation (c.

Identification of steroid biosynthetic defects in genotype-proven heterozygous individuals for 17alpha-hydroxylase/17,20-lyase deficiency.

Objective: P450c17 deficiency (17alpha-hydroxylase/17,20-lyase deficiency, 17OHD) is a rare form of congenital adrenal hyperplasia caused by CYP17A1 gene mutations. The D487_F489 deletion in exon 8 and Y329fs in exon 6 are relatively frequent mutations of the CYP17A1 gene in China that completely abolish the enzyme activity of P450c17. However, little remains known about steroid biosynthetic functions in carriers with these mutations in a single allele of the CYP17A1 gene, who are assumed to have 50% P450c17 activity.

Efficacy and safety of 2 g/day of strontium ranelate in Asian women with postmenopausal osteoporosis.

Strontium ranelate is a new effective anti-osteoporotic treatment having a unique mode of action, reducing bone resorption while promoting continued bone formation, with a broad range of anti-fracture efficacy at vertebral as well as peripheral sites. In Phase III studies, it has proven its early and sustained efficacy against vertebral fractures in Caucasians along with a significant increase in lumbar bone mineral density (BMD). The aim of this randomized double-blind study was to demonstrate the efficacy of strontium ranelate (2 g/day) on lumbar spine bone mineral density and the clinical and biological safety in Asian postmenopausal osteoporotic patients compared to placebo over 1 year.

Functional SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves' disease.

Graves' disease (GD) is one of the most common human autoimmune diseases, and recent data estimated a prevalence of clinical hyperthyroidism of 0.25-1.09% in the population.

IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women.

To find out which of the following parameters-serum levels of insulin-like growth factor 1 (IGF-1), osteoprotegerin (OPG), leptin, osteocalcin (OC), and urinary excretion of N-terminal telopeptide of type I collagen (NTx), can be used as an early marker for osteopenia/osteoporosis in women diagnosed by dual-energy X-ray absorptiometry (DXA), 282 premenopausal and 222 postmenopausal women aged 20-75 years were investigated by the measurement of bone mineral densities (BMDs) at lumbar spine (LS) and femoral neck (FN) by DXA, together with serum concentrations of IGF-1, OPG, leptin, OC, and urinary NTx. The characteristics of the earliest marker(s) were tested with the receiver operating characteristic (ROC) analysis. The area under the curve (AUC), sensitivity, and specificity parameters were determined.

Interleukin-18 enhances glucose uptake in 3T3-L1 adipocytes.

In order to characterize the potential causative effects of interleukin-18 (IL-18) on insulin resistance, we measured glucose uptake in 3T3-L1 adipocytes treated with mouse recombinant IL-18. IL-18 surprisingly enhanced, rather than reduced insulin-mediated glucose uptake in adipocytes. Moreover IL-18 could counteract the glucose uptake suppression caused by tumor necrosis factor alpha in 3T3-L1 adipocytes.

Effect of short-term and long-term fasting on transcriptional regulation of metabolic genes in rat tissues.

Ninety-eight genes/ESTs with differential expressions in epididymal adipose tissue of fed and 3-day fasting (F3) rats were identified by microarray analysis. Genes for lipogenesis, glycolysis, and glucose aerobic oxidation were decreased in response to starvation. Further study was performed to investigate the expression patterns of these genes in rat tissues after short- and long-term starvations.

[Study of the impact of candidate genes on bone mineral density in postmenopausal women].

Objective: To investigate the impact of multiple candidate genes on bone mineral density in postmenopausal women.

Methods: Bone mineral density (BMD) at lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry (DEXA) in 205 postmenopausal women. Polymerase chain reaction (PCR) and direct sequencing technique were used to identify osteoprotegerin gene polymorphism.

The mimecan gene expressed in human pituitary and regulated by pituitary transcription factor-1 as a marker for diagnosing pituitary tumors.

Context: Mimecan, a secretory protein, belongs to a family of small leucine-rich proteoglycans (SLRPs). The physiological functions of mimecan have not been fully understood.

Objective: We hypothesize that the mimecan gene expressed in the human pituitary and regulated by pituitary transcription factor-1 (Pit-1) might act as a marker for diagnosing pituitary tumors.

Structure and functional analysis of unclassified genes strongly expressed in human visceral adipose tissue.

Our previous work has described the gene expression patterns of human visceral adipose tissue (VAT) at the transcriptome level and reported that the strongly expressed genes in VAT showed an uneven distribution throughout the genome. The aim of the present work was to focus on the unclassified genes and known expressed sequence tags (ESTs) strongly expressed in VAT and analyze their structure and function with bioinformatics. Among the 400 ESTs strongly expressed in the VAT, 340 clones were classified into known genes through searching the latest Genbank database.

The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women.

The objective was to identify single nucleotide polymorphisms (SNPs) in exons of the osteoprotegerin gene and to analyze the relationship between the SNPs and bone mineral density in postmenopausal women. We used polymerase chain reaction (PCR) and direct sequencing methods to identify SNPs and genotypes in 205 postmenopausal women. BMD at the lumbar spine (L2-4) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry (DEXA).

[The relationships between changes of serum osteoprotegerin, nuclear factor-kappa B ligand receptor activator, and age, menopause, bone biochemical markers and bone mineral densities in women aged 20 - 75].

Objective: To investigate the relationships between the serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL) with age, menopause, bone biochemical markers and bone mineral densities (BMDs) in pre- and postmenopausal women and to determine the contributing factors for serum OPG and RANKL.

Methods: 504 pre- and postmenopausal women aged between 20 and 75 years were enrolled in this study. BMDs at lumbar spine and proximal femur were measured with dual-energy X-ray absorption meter.

[The relationship between body composition measured with bioelectric impedance analysis and bone mass in female].

Objective: To investigate the effect of fat mass and fat-free mass on bone mineral density (BMD) in pre- and postmenopausal women.

Methods: 282 premenopausal women with regular menstruation and 205 postmenopausal women were enrolled in this study. BMD at lumbar spine (L(2 - 4)) and femoral neck (FN) were measured with dual-energy X-ray absorptiometry (DEXA).

Relationship between body composition and bone mineral density in healthy young and premenopausal Chinese women.

This study investigated the relative contribution of fat mass and lean mass to bone mineral density (BMD) in young and premenopausal healthy Chinese women. The study was performed in 282 young and premenopausal healthy women with regular menstrual cycles. The BMD at lumbar spine (L2-L4), total hip and total body, together with fat mass and lean mass were assessed by dual-energy X-ray absorptiometry (DXA); body height, weight, waist and hip circumference were also measured, and body mass index (BMI) and waist-hip ratio were calculated.