LHB
Lutropin subunit beta precursor (Lutropin beta chain) (Luteinizing hormone subunit beta) (LH-B) (LSH-B) (LSH-beta)
Publications[править]
Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. A total of 2748 men, aged 40-79 (mean /- sd, 60.2 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
MeSH Terms
- Adult
- Aged
- Aging
- Cohort Studies
- Cross-Sectional Studies
- DNA
- Databases, Genetic
- Europe
- Gene Frequency
- Genotype
- Gonadal Steroid Hormones
- Health Status
- Humans
- Male
- Middle Aged
- Phenotype
- Pituitary Gland
- Polymorphism, Genetic
- Polymorphism, Single Nucleotide
- Prospective Studies
- Sex Hormone-Binding Globulin
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Testis
Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle-aged and elderly European men. Men 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB, and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 /- 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0 /- 18.9 dB/Mhz, SOS was 1550.2 /- 34.1 m/s, and BMD was 0.542 /- 0.141 g/cm(2). Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta =-0.016, p = -0.005) and homozygotes (beta = -0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR, and ESR1. Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP19A1, as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR, and AR in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.
MeSH Terms
- Aged
- Aging
- Aromatase
- Bone Density
- Calcaneus
- European Continental Ancestry Group
- Genetic Variation
- Genotype
- Gonadal Steroid Hormones
- Humans
- Male
- Middle Aged
- Polymorphism, Genetic
- Repetitive Sequences, Nucleic Acid
- Ultrasonography