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Genetic determinants of serum testosterone concentrations in men
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نویسنده
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ohlsson c. ,wallaschofski h. ,lunetta k.l. ,stolk l. ,perry j.r.b. ,koster a. ,petersen a.-k. ,eriksson j. ,lehtimäki t. ,huhtaniemi i.t. ,hammond g.l. ,maggio m. ,coviello a.d. ,emas study group the european male ageing study ,ferrucci l. ,heier m. ,hofman a. ,holliday k.l. ,jansson j.-o. ,kähönen m. ,karasik d. ,karlsson m.k. ,kiel d.p. ,liu y. ,ljunggren o. ,lorentzon m. ,lyytikäinen l.-p. ,meitinger t. ,mellström d. ,melzer d. ,miljkovic i. ,nauck m. ,nilsson m. ,penninx b. ,pye s.r. ,vasan r.s. ,reincke m. ,rivadeneira f. ,tajar a. ,teumer a. ,uitterlinden a.g. ,ulloor j. ,viikari j. ,völker u. ,völzke h. ,wichmann h.e. ,wu t.-s. ,zhuang w.v. ,ziv e. ,wu f.c.w. ,raitakari o. ,eriksson a. ,bidlingmaier m. ,harris t.b. ,murray a. ,de jong f.h. ,murabito j.m. ,bhasin s. ,vandenput l. ,haring r.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 10
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چکیده
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Testosterone concentrations in men are associated with cardiovascular morbidity,osteoporosis,and mortality and are affected by age,smoking,and obesity. because of serum testosterone's high heritability,we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. all these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. two single-nucleotide polymorphisms at the sex hormone-binding globulin (shbg) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660,p = 1.2×10 -41 and rs6258,p = 2.3×10 -22). subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. the rs5934505 polymorphism near fam9b on the x chromosome was also associated with testosterone concentrations (p = 5.6×10 -16). the rs6258 polymorphism in exon 4 of shbg affected shbg's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). genetic variants in the shbg locus and on the x chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported shbg polymorphism,which affects testosterone binding to shbg and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
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آدرس
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center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, institute of clinical chemistry and laboratory medicine,university of greifswald,greifswald, Germany, the national heart,lung,blood institute's framingham heart study,framingham,ma,united states,department of biostatistics,boston university school of public health,boston,ma, United States, department of internal medicine,erasmus mc rotterdam,rotterdam,netherlands,netherlands consortium of healthy ageing,rotterdam, Netherlands, genetics of complex traits,peninsula medical school,university of exeter,exeter,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, laboratory for epidemiology,demography,and biometry,national institute on aging,bethesda,md, United States, institute of genetic epidemiology,helmholtz zentrum münchen,neuherberg, Germany, center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of clinical chemistry,university of tampere,tampere university hospital,tampere, Finland, department of surgery and cancer,imperial college london,hammersmith campus,london, United Kingdom, child and family research institute,department of obstetrics and gynecology,university of british columbia,vancouver, Canada, departments of internal medicine and biomedical sciences,section of geriatrics,university of parma,parma, Italy, the national heart,lung,blood institute's framingham heart study,framingham,ma,united states,sect. of gen. internal med.,preventive med.,cardiology,and endocrinology,diabetes,and nutrition,department of medicine,boston university school of medicine,boston,ma, United States, university of manchester,manchester, United Kingdom, longitudinal studies section,clinical research branch,national institute on aging,baltimore,md, United States, institute of epidemiology ii,helmholtz zentrum münchen,neuherberg, Germany, netherlands consortium of healthy ageing,rotterdam,netherlands,department of epidemiology,erasmus mc rotterdam,rotterdam, Netherlands, arthritis research uk epidemiology unit,university of manchester,manchester academic health science centre,manchester, United Kingdom, department of physiology,institute of neuroscience and physiology,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of clinical physiology,university of tampere,tampere university hospital,tampere, Finland, hebrew seniorlife institute for aging research,harvard medical school,boston,ma, United States, clinical and molecular osteoporosis research unit,department of clinical sciences and department of orthopaedics,lund university,skane university hospital,malmö, Sweden, the national heart,lung,blood institute's framingham heart study,framingham,ma,united states,hebrew seniorlife institute for aging research,harvard medical school,boston,ma, United States, department of epidemiology and prevention,wake forest university health sciences,winston-salem,nc, United States, department of medical sciences,university of uppsala,uppsala, Sweden, center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of clinical chemistry,university of tampere,tampere university hospital,tampere, Finland, institute of human genetics,technische universität münchen,münchen,germany,institute of human genetics,helmholtz zentrum münchen,neuherberg, Germany, center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, peninsula medical school,university of exeter,exeter, United Kingdom, university of pittsburgh,department of epidemiology,pittsburgh,pa, United States, institute of clinical chemistry and laboratory medicine,university of greifswald,greifswald, Germany, center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of psychiatry and emgo institute for health and care research,vu university medical center,amsterdam, Netherlands, arthritis research uk epidemiology unit,university of manchester,manchester academic health science centre,manchester, United Kingdom, the national heart,lung,blood institute's framingham heart study,framingham,ma,united states,sect. of gen. internal med.,preventive med.,cardiology,and endocrinology,diabetes,and nutrition,department of medicine,boston university school of medicine,boston,ma, United States, medizinische klinik innenstadt,ludwig-maximilians-university,münchen, Germany, department of internal medicine,erasmus mc rotterdam,rotterdam,netherlands,netherlands consortium of healthy ageing,rotterdam,netherlands,department of epidemiology,erasmus mc rotterdam,rotterdam, Netherlands, arthritis research uk epidemiology unit,university of manchester,manchester academic health science centre,manchester, United Kingdom, interfaculty institute for genetics and functional genomics,university of greifswald,greifswald, Germany, department of internal medicine,erasmus mc rotterdam,rotterdam,netherlands,netherlands consortium of healthy ageing,rotterdam,netherlands,department of epidemiology,erasmus mc rotterdam,rotterdam, Netherlands, sect. of gen. internal med.,preventive med.,cardiology,and endocrinology,diabetes,and nutrition,department of medicine,boston university school of medicine,boston,ma, United States, department of medicine,university of turku,turku university hospital,turku, Finland, interfaculty institute for genetics and functional genomics,university of greifswald,greifswald, Germany, institute for community medicine,university of greifswald,greifswald, Germany, institute of medical informatics,biometry and epidemiology,ludwig-maximilians-university,münchen,germany,klinikum großhadern,münchen,germany,institute of epidemiology i,helmholtz zentrum münchen,neuherberg, Germany, child and family research institute,department of obstetrics and gynecology,university of british columbia,vancouver, Canada, department of biostatistics,boston university school of public health,boston,ma, United States, division of general internal medicine,department of medicine,university of california san francisco,san francisco,ca,united states,department of epidemiology and biostatistics,institute for human genetics,university of california san francisco,san francisco,ca, United States, andrology research unit,developmental and regenerative biomedicine research group,the university of manchester,manchester academic health science centre,manchester royal infirmary,manchester, United Kingdom, research centre of applied and preventive cardiovascular medicine,university of turku,finland,department of clinical physiology,turku university hospital,turku, Finland, center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, medizinische klinik innenstadt,ludwig-maximilians-university,münchen, Germany, laboratory for epidemiology,demography,and biometry,national institute on aging,bethesda,md, United States, genetics of complex traits,peninsula medical school,university of exeter,exeter,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, department of internal medicine,erasmus mc rotterdam,rotterdam, Netherlands, the national heart,lung,blood institute's framingham heart study,framingham,ma,united states,sect. of gen. internal med.,preventive med.,cardiology,and endocrinology,diabetes,and nutrition,department of medicine,boston university school of medicine,boston,ma, United States, the national heart,lung,blood institute's framingham heart study,framingham,ma,united states,sect. of gen. internal med.,preventive med.,cardiology,and endocrinology,diabetes,and nutrition,department of medicine,boston university school of medicine,boston,ma, United States, center for bone and arthritis research,department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, institute of clinical chemistry and laboratory medicine,university of greifswald,greifswald, Germany
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Authors
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