Dataset Information

Socioeconomic Deprivation as Measured by the Index of Multiple Deprivation and Its Association with Low Sex Hormone Binding Globulin in Women.

ABSTRACT: OBJECTIVE:Sex hormone binding globulin (SHBG) is a marker of insulin resistance. Given established links between BMI and socioeconomic disadvantage, we investigated how SHBG varies by index of multiple deprivation (IMD). RESEARCH DESIGN AND METHODS:Using laboratory data from a Midlands UK population of mixed ethnicity, we examined the relation between blood concentrations of SHBG and IMD in 1160 women aged between 17 and 71 years. Women with a serum SHBG >250 nmol/L were excluded. RESULTS:Mean age was 28.7 (95% confidence interval (CI) 28.2-29.1) years. 48.2% of women were of Caucasian origin, 15.5% of Southern Asian ethnicity and 2.6% were of African or other origin (33.7% were of unknown origin). SHBG increased with age (Spearman's ?=0.195; p<0.001). A higher proportion of women of South Asian origin versus other ethnic groups had an SHBG <30 nmol/L (OR 1.93 (95% CI 1.37-2.71)). SHBG level was lower in individuals with greater socioeconomic disadvantage as measured by IMD (Spearman's ?= -0.09; p=0.004 for SHBG versus IMD). In multivariate logistic regression, IMD women in the quartiles 2-5 (higher socioeconomic disadvantage) were more likely to have an SHBG <30 nmol/L (compatible with significant insulin resistance) versus quartile 1 (odds ratio (OR) 1.71 (95% confidence interval (CI) 1.17-2.53), adjusted for age (OR=0.97 (95% CI 0.95-0.98)) and ethnicity (for South Asian ethnicity OR=2.00 (95% CI 1.42-2.81) versus the rest). CONCLUSION:Lower SHBG levels in women are associated with a higher level of socioeconomic disadvantage. Given the known association between lower SHBG and higher plasma glucose, our findings suggest a link between socioeconomic disadvantage and future risk of type 2 diabetes.

SUBMITTER: Heald A

PROVIDER: S-EPMC5388792 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Socioeconomic Deprivation as Measured by the Index of Multiple Deprivation and Its Association with Low Sex Hormone Binding Globulin in Women.

Heald Adrian A Laing Ian I McLernon David J DJ Donn Rachelle R Hartland Andrew J AJ Fryer Anthony A AA Livingston Mark M

The open biochemistry journal 20170313

<h4>Objective</h4>Sex hormone binding globulin (SHBG) is a marker of insulin resistance. Given established links between BMI and socioeconomic disadvantage, we investigated how SHBG varies by index of multiple deprivation (IMD).<h4>Research design and methods</h4>Using laboratory data from a Midlands UK population of mixed ethnicity, we examined the relation between blood concentrations of SHBG and IMD in 1160 women aged between 17 and 71 years. Women with a serum SHBG >250 nmol/L were excluded. ...[more]

PMID: 28458728

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Project description:BackgroundCirculating sex hormone-binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain.MethodsWe performed a nested case-control study of postmenopausal women in the Women's Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone-binding globulin were measured; two polymorphisms of the gene encoding sex hormone-binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians' Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls).ResultsAmong women, higher plasma levels of sex hormone-binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone-binding globulin levels (P=0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P=0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone-binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex hormone-binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex hormone-binding globulin may have a causal role in the risk of type 2 diabetes.ConclusionsLow circulating levels of sex hormone-binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination.

Project description: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.

Dataset Information

Socioeconomic Deprivation as Measured by the Index of Multiple Deprivation and Its Association with Low Sex Hormone Binding Globulin in Women.

Publications

Socioeconomic Deprivation as Measured by the Index of Multiple Deprivation and Its Association with Low Sex Hormone Binding Globulin in Women.

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