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- Eriksson, Anna-Lena, 1971, et al.
(author)
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Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men.
- 2018
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:3, s. 991-1004
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Journal article (peer-reviewed)abstract
- Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability.To investigate the genetic regulation of serum E2 and E1 in men.Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts.Genetic determinants of serum E2 and E1 levels.Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance.Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.
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- von Berens, Åsa, et al.
(author)
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Physical performance and serum 25(OH)vitamin D status in community dwelling old mobility limited adults : A cross-sectional study
- 2018
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In: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 22:1, s. 1-7
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Journal article (peer-reviewed)abstract
- Objectives:To examine the potential association between serum 25(OH) vitamin D and theperformance on the Short Physical Performance Battery (SPPB) including the sub-components; five repeatedchair stands test, 4 meters walk test and balance in older mobility-limited community-dwelling men and women.Design:A cross sectional study was performed in American and Swedish subjects who were examined forpotential participation in a combined exercise and nutrition intervention trial. Logistic regression analysis andlinear regression analyses were performed to evaluate the association for 25(OH)D with the overall score onthe SBBP, chair stand, gait speed and balance.Participants:Community-dwelling (mean age 77.6 ± 5.3 years)mobility limited American (n=494) and Swedish (n=116) females (59%) and males.Measurements:The SPPB(0-12 points) includes chair stand (s), gait speed (m/s) and a balance test. Mobility limitation i.e., SPPB score ≤9 was an inclusion criterion. A blood sample was obtained to measure serum 25(OH)vitamin D concentrations.Results:No clear association of 25(OH)D with SPPB scores was detected either when 25(OH)D was assessedas a continuous variable or when categorized according to serum concentrations of <50, 50-75 or <75 nmol/L.However, when analyzing the relationship between 25(OH)D and seconds to perform the chair stands, asignificant quadratic relationship was observed. Thus, at serum levels of 25(OH)D above 74 nmol/L, higherconcentrations appeared to be advantageous for the chair stand test, whereas for serum levels below 74 nmol/Lthis association was not observed.Conclusion: This cross- sectional study lacked clear association betweenserum 25(OH)D and physical performance in mobility limited adults. A potentially interesting observation wasthat at higher serum levels of 25(OH)D a better performance on the chair stand test was indicated.
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