Preclinical metabolism and disposition of [C]GFH009, a novel selective CDK9 inhibitor.

GFH009 is a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor currently under phase II clinical trials. In this study, we investigated the metabolism and disposition of GFH009 in Sprague-Dawley (SD) rats, as well as metabolism of CD-1 mouse, SD rat, beagle dog, cynomolgus monkey, and human.A radiolabelled study indicated that [C]GFH009 was quickly and widely distributed throughout the body, but presented low levels in brain, testis, and epididymis after a single intravenous dose of 6 mg (100 µCi)/kg to SD rats.

Development and validation of a sensitive UPLC-MS/MS analytical method for GFH009 in rat plasma and its application to toxicokinetics studies.

GFH009 is a potent, highly selective, small molecule that targets and inhibits the activity of the CDK9/cyclin T1 regulatory complex of P-TEFb. This study aimed to develop and validate a highly selective and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for precise quantification of GFH009 in rat plasma. This method was subsequently employed for conducting toxicokinetic studies of GFH009 in rats.

A Common Variant at 11q23.3 Is Associated with Susceptibility to Atopic Dermatitis in the Han Chinese Population.

Genome-wide association studies (GWASs) have identified many genetic variants that are risk factors for numerous immune-mediated diseases. In particular, different immune-mediated diseases have been found to share the same susceptibility loci. Therefore, exploring the genetic overlap between atopic dermatitis (AD) and other immune-mediated diseases in more detail may help identify additional shared susceptibility loci among common immune-mediated diseases.

C-reactive protein/abumin ratio is a useful biomarker for predicting the mucosal healing in the Crohn disease: A retrospective study.

Ileocolonoscopy is currently recognized as the gold standard for evaluating mucosal healing in patients with Crohn disease (CD). However, the ideal noninvasive marker to assess mucosal healing instead of invasive ileocolonoscopy is not available. This study aimed to determine the correlations between the mucosal healing and serological optimizing markers in CD.

Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population.

Forty-nine susceptible loci have been reported to be significantly associated with vitiligo by genome-wide association studies (GWASs) in European-derived whites. To date, some of these reported susceptibility loci have not yet been validated in the Chinese Han population. The purpose of this study was to examine whether the 16 reported susceptible loci in European-derived whites were associated with vitiligo in the Chinese Han population.

GWAS Follow-up Study Discovers a Novel Genetic Signal on 10q21.2 for Atopic Dermatitis in Chinese Han Population.

Atopic dermatitis (AD) is a common inflammatory skin disease with high heritability. Two susceptibility loci have been confirmed in our previous AD genome-wide association study (GWAS). To look for additional genetic factors in Chinese Han ethnicity, we performed a large-scale GWAS follow-up study.

Novel mutations in Chinese Han patients with tuberous sclerosis complex: Case series and review of the published work.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease characterized by hamartomas in multiple organ systems. This study was performed in one familial and two sporadic cases with TSC. Two novel mutations (c.

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls).

A variant on chromosome 2p13.3 is associated with atopic dermatitis in Chinese Han population.

Background: Multi-ancestry genome-wide association study (GWAS) has recently identified 11 new susceptibility loci for Atopic dermatitis (AD). The replication of these new susceptibility loci in different populations should not be ignored.

Objective: To examine whether these 11 new identified susceptibility loci are also associated with AD in the Chinese Han population.

Association analyses identify two susceptibility loci 5q31 and 5q22.1 for atopic dermatitis in Chinese Han population.

Background: Atopic dermatitis (AD) and other atopic diseases often share some common genetic and pathogenic bases. Recent genome-wide association studies (GWAS) have identified several loci associated with atopic diseases, allergic sensitization and asthma in different populations. The aim of this study was to investigate whether these susceptibility loci were related to AD in Chinese Han population.

Scanning indels in the 5q22.1 region and identification of the TMEM232 susceptibility gene that is associated with atopic dermatitis in the Chinese Han population.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. The 5q22.1 region was found to have an association with AD in our previous genome-wide association study (GWAS).

Association of the chromosome 11p13.5 variant and atopic dermatitis with a family history of atopy in the Chinese Han population.

Background: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations.

Objective: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population.

Methods: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform.

Increased expression of IL-28RA mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune and inflammatory disease with a strong genetic contribution and characterized by kinds of immune reactions. Our previous genome-wide association studies have identified IL-28RA as a susceptibility gene for SLE. In this study, we performed a quantitative reverse transcription polymerase chain reaction (RT-PCR) in 62 patients with SLE and 69 controls to investigate the different expression levels of IL-28RA in peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls and the association between IL-28RA expression and systemic lupus erythematosus disease activity index (SLEDAI) or the variant of the single-nucleotide polymorphism (SNP) rs4649203.

Association analyses confirm five susceptibility loci for systemic lupus erythematosus in the Han Chinese population.

Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study.

Association of genetic variants in SOHLH1 and SOHLH2 with non-obstructive azoospermia risk in the Chinese population.

Objective: Spermatogenesis and oogenesis specific basic helix-loop-helix 1 (SOHLH1) and spermatogenesis and oogenesis specific basic helix-loop-helix 2 (SOHLH2) play essential roles for both spermatogenesis and oogenesis. The aim of this study was to evaluate the association of SOHLH1 and SOHLH2 single nucleotide polymorphisms (SNPs) with non-obstructive azoospermia (NOA) in the Chinese population.

Study Design: In this study, we assessed 7 single nucleotide polymorphisms (SNPs) of SOHLH1 and SOHLH2 with Sequenom iplex technology in 361 NOA cases and 368 fertile controls.

Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3 genes with non-obstructive azoospermia in the Chinese population.

Purpose: To research the association between the single nucleotide polymorphisms (SNPs) of three spermatogenesis-related genes (USF1, GTF2A1L and OR2W3) and non-obstruction azoospermia (NOA).

Methods: We investigated 361 NOA cases and 368 controls from the Chinese Han population, and we used Sequenom iplex technology to analyze the candidate 9 SNPs from the USF1, GTF2A1L and OR2W3 genes.

Results: In this study, we found that the variant rs2516838 of USF1 was associated with NOA susceptibility (P = 0.

Association study of susceptibility loci with specific breast cancer subtypes in Chinese women.

To determine whether recent genome-wide association studies that reported 45 susceptibility loci in European women are also risk factors for breast cancer in Chinese women. We selected and genotyped 40 single nucleotide polymorphisms (SNPs) using the Sequenom iPlex platform in a female Chinese cohort of 2,901 breast cancer cases and 2,789 healthy controls. We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor (ER) status, progestin (PR) status, human epidermal growth factor receptor-2 (HER-2) status, and four breast cancer subtypes (Luminal A type, Luminal B type, HER-2 overexpression type and Basal-like type).

CREM variants rs4934540 and rs2295415 conferred susceptibility to nonobstructive azoospermia risk in the Chinese population.

To evaluate the association of variants related to spermatogenesis with susceptibility to Chinese idiopathic nonobstructive azoospermia (NOA), seventeen tag single-nucleotide polymorphisms (SNPs) in CREM, ACT, KIF17b, and SPAG8 were analyzed in 361 NOA patients and 368 controls by Sequenom iplex technology. The results showed that two CREM SNPs, rs4934540 and rs22954152, were significantly associated with NOA and played protective roles against the disease (P value with Bonferroni correction = 0.00017, odds ratio [OR] = 0.

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne.

Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association.