Dataset Information

Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.

ABSTRACT: Several members of the EPH kinase family and their ligands are involved in blood pressure regulation, and such regulation is often sex- or sex hormone-dependent, based on animal and human genetic studies. EPHB6 gene knockout (KO) in mice leads to hypertension in castrated males but not in un-manipulated KO males or females. To assess whether this finding in mice is relevant to human hypertension, we conducted a human genetic study for the association of EPHB6 and its two ligands, EFNB1 and EFNB3, with hypertension in hypogonadic patients. Seven hundred and fifty hypertensive and 750 normotensive Han Chinese patients, all of whom were hypogonadic, were genotyped for single nucleotide polymorphisms (SNPs) within the regions of the genes, plus an additional 50?kb 5' of the genes for EPHB6, EFNB1 and EFNB3. An imputed insertion/deletion polymorphism, rs35530071, was found to be associated with hypertension at p-values below the Bonferroni-corrected significance level of 0.0024. This marker is located 5' upstream of the EFNB3 gene start site. Previous animal studies showed that while male EFNB3 gene knockout mice were normotensive, castration of these mice resulted in hypertension, corroborating the results of the human genetic study. Considering the significant associations of EFNB3 SNPs with hypertension in hypogonadic males and supporting evidence from castrated EFNB3 KO mice, we conclude that loss-of-function variants of molecules in the EPHB6 signaling pathway in the presence of testosterone are protective against hypertension in humans.

SUBMITTER: Wu T

PROVIDER: S-EPMC6160468 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.

Wu Tao T Zhang Bi-Qi BQ Raelson John J Yao Yu-Mei YM Wu Huan-Dong HD Xu Zao-Xian ZX Marois-Blanchet Francois-Christophe FC Tahir Muhammad Ramzan MR Wang Yujia Y Bradley W Edward WE Luo Hongyu H Wu Jiangping J Sheng Jian-Zhong JZ Hu Shen-Jiang SJ

Scientific reports 20180927 1

Several members of the EPH kinase family and their ligands are involved in blood pressure regulation, and such regulation is often sex- or sex hormone-dependent, based on animal and human genetic studies. EPHB6 gene knockout (KO) in mice leads to hypertension in castrated males but not in un-manipulated KO males or females. To assess whether this finding in mice is relevant to human hypertension, we conducted a human genetic study for the association of EPHB6 and its two ligands, EFNB1 and EFNB3 ...[more]

PMID: 30262919

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Project description:For decades researchers have reported men who engaged in intensive exercise training can develop low resting testosterone levels, alterations in their hypothalamic-pituitary-gonadal (HPG) axis, and display hypogonadism. Recently there is renewed interest in this topic since the International Olympic Committee (IOC) Medical Commission coined the term "Relative Energy Deficiency in Sports" (RED-S) as clinical terminology to address both the female-male occurrences of reproductive system health disruptions associated with exercise. This IOC Commission action attempted to move beyond the sex-specific terminology of the "Female Athlete Triad" (Triad) and heighten awareness/realization that some athletic men do have reproductive related physiologic disturbances such as lowered sex hormone levels, HPG regulatory axis alterations, and low bone mineral density similar to Triad women. There are elements in the development and symptomology of exercise-related male hypogonadism that mirror closely that of women experiencing the Triad/RED-S, but evidence also exists that dissimilarities exist between the sexes on this issue. Our research group postulates that the inconsistency and differences in the male findings in relation to women with Triad/RED-S are not just due to sex dimorphism, but that there are varying forms of exercise-related reproductive disruptions existing in athletic men resulting in them displaying a relative hypogonadism condition. Specifically, such conditions in men may derive acutely and be associated with low energy availability (Triad/RED-S) or excessive training load (overtraining) and appear transient in nature, and resolve with appropriate clinical interventions. However, manifestations of a more chronic based hypogonadism that persists on a more permanent basis (years) exist and is termed the "Exercise Hypogonadal Male Condition." This article presents an up-to-date overview of the various types of acute and chronic relative hypogonadism found in athletic, exercising men and proposes mechanistic models of how these various forms of exercise relative hypogonadism develop.

Dataset Information

Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.

Publications

Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.

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