Androgenic correlates of genetic variation in the gene encoding 5alpha-reductase type 1.
Androgens determine male secondary sexual characteristics and influence a variety of metabolic pathways. Circulating levels of androgens are highly heritable; however, the genes involved are largely unknown. The 5alpha-reductase enzymes types 1 and 2 responsible for converting testosterone to the more potent androgen dihydrotestosterone are encoded by the SRD5A1 and SRD5A2 genes, respectively. We performed indirect genetic association studies of SRD5A1 and SRD5A2 and the dihydrotestosterone/testosterone ratio that reflects the activity of 5alpha-reductase in 57 males with type 2 diabetes. We found evidence of significant association between a single nucleotide polymorphism in SRD5A1 and the dihydrotestosterone/testosterone ratio (median 0.10, interquartile range 0.08 vs. median 0.06, interquartile range 0.04, P = 0.009). The polymorphism was not associated with any diabetic phenotypes. These results suggest that functional genetic variants might exist in or around SRD5A1 that affect the activity of the 5alpha-reductase enzyme type 1 and influence androgen levels.
Ellis
Justine A
JA
Department of Physiology, The University of Melbourne, Melbourne, Victoria, 3010, Australia. justine@unimelb.edu.au.
Panagiotopoulos
Sianna
S
Endocrinology Unit, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia.
Akdeniz
Aysel
A
Endocrinology Unit, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia.
Jerums
George
G
Endocrinology Unit, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia.
Harrap
Stephen B
SB
Department of Physiology, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood* / Q000235:genetics; D042944:Cholestenone 5 alpha-Reductase / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics; D013196:Dihydrotestosterone / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013739:Testosterone / Q000097:blood* / Q000235:genetics
D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D042944:Cholestenone 5 alpha-Reductase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase