title: Estrogen receptor alpha single nucleotide polymorphism as predictor of diabetes type 2 risk in hypogonadal men.
abstract: Estradiol (E2) is, apart from its role as a reproductive hormone, also important for cardiac function and bone maturation in both genders. It has also been shown to play a role in insulin production, energy expenditure and in inducing lipolysis. The aim of the study was to investigate if low circulating testosterone or E2 levels in combination with variants in the estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) genes were of importance for the risk of type-2 diabetes. The single nucleotide polymorphisms rs2207396 and rs1256049, in ESR1 and ESR2, respectively, were analysed by allele specific PCR in 172 elderly men from the population-based Tromsø study. The results were adjusted for age. In individuals with low total (≤11 nmol/L) or free testosterone (≤0.18 nmol/L) being carriers of the variant A-allele in ESR1 was associated with 7.3 and 15.9 times, respectively, increased odds ratio of being diagnosed with diabetes mellitus type 2 (p = 0.025 and p = 0.018, respectively). Lower concentrations of E2 did not seem to increase the risk of being diagnosed with diabetes. In conclusion, in hypogonadal men, the rs2207396 variant in ESR1 predicts the risk of type 2 diabetes.
authors.affiliation: Department of Clinical Sciences, Molecular Genetic Reproductive Medicine, Lund University, Malmö, Sweden. carl.linner@med.lu.se
authors.forename: Carl
authors.initials: C
authors.lastname: Linnér
authors.forename: Johan
authors.initials: J
authors.lastname: Svartberg
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.forename: Yvonne Lundberg
authors.initials: YL
authors.lastname: Giwercman
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000483:Alleles; D015331:Cohort Studies; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D013739:Testosterone / Q000097:blood
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013739:Testosterone