| 1. |
- Andersson, Niklas, 1970, et al.
(författare)
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A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
- 2010
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:6, s. 1011-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.
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| 2. |
- Atroshi, Isam, et al.
(författare)
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Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study.
- 2009
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:4, s. 789-93
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score< or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.
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| 3. |
- Bentmar Holgersson, Magdalena, et al.
(författare)
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Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele
- 2017
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Ingår i: Cancer Causes & Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 28:3, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Using data from two population-based cohorts; the Malmo Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45-0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47-1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51-0.90; p = 0.008). Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.
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| 4. |
- Björk, Anne, et al.
(författare)
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Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD). Methods Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69–81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years. Results There was a significant genetic association with circulating levels of 25(OH)D (4.6–18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005). Conclusions Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.
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| 5. |
- Björk, Anne, et al.
(författare)
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Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men : Data from MrOS Sweden
- 2019
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 187, s. 160-165
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Tidskriftsartikel (refereegranskat)abstract
- The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.
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| 6. |
- Bokrantz, Tove, et al.
(författare)
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The association between peripheral arterial disease and risk for hip fractures in elderly men is not explained by low hip bone mineral density. Results from the MrOS Sweden study
- 2022
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective study in Swedish elderly men, PAD based on an ABI < 0.9 was associated with an increased risk of hip fracture, independent of age and hip BMD. However, after further adjustments for comorbidity, medications, physical function, and socioeconomic factors, the association diminished and was no longer statistically significant. Introduction To examine if peripheral arterial disease (PAD) is associated with an increased risk for hip fracture in men independent of hip BMD. Methods Ankle-brachial index (ABI) was assessed in the Swedish MrOS (Osteoporotic Fractures in Men) study, a prospective observational study including 3014 men aged 69-81 years at baseline. PAD was defined as ABI < 0.90. Incident fractures were assessed in computerized X-ray archives. The risk for hip fractures was calculated using Cox proportional hazard models. At baseline, BMD was assessed using DXA (Lunar Prodigy and Hologic QDR 4500) and functional measurements and blood samples were collected. Standardized questionnaires were used to collect information about medical history, falls, and medication. Results During 10 years of follow-up, 186 men had an incident hip fracture. The hazard ratio (HR) for hip fracture in men with PAD was 1.70 (95% CI 1.14-2.54), adjusted for age and study site. Additional adjustment for total hip BMD marginally affected this association (HR 1.64; 95% CI 1.10-2.45). In a final multivariate model, the HR attenuated to a non-significant HR 1.38 (95% CI 0.91-2.11) adjusted for age, site, hip BMD, BMI, falls, smoking, eGFR, handgrip strength, walking speed, former hip fracture, antihypertensive treatment, diabetes, education, and history of cardiovascular disease. Conclusion This study suggests that PAD is associated with an increased risk for hip fracture independently of hip BMD in elderly Swedish men. However, the high frequency of comorbidity and lower physical performance among men with PAD might partly explain this association.
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| 7. |
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| 8. |
- Cawthon, Peggy M, et al.
(författare)
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What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 76:10, s. e321-e327
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Tidskriftsartikel (refereegranskat)abstract
- Cut-points to define slow walking speed have largely been derived from expert opinion.Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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| 9. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4×10(-11)), GCKR (rs780093, 2p23.3, p = 2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 10. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:3, s. 1033-41
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids. OBJECTIVE: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men. DESIGN: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 +/- 0.6 yr). Replications of significant associations were performed in the Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 +/- 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 +/- 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry. RESULTS: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1, to be most significantly associated with serum E2 levels (P = 2 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). CONCLUSIONS: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
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