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 = 1.8x10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4x10(-11)), GCKR (rs780093, 2p23.3, p=2.2x10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4x10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1x10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9x10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3x10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5x10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1x10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3x10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7x10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5x10(-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 = 2.5x10(-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 similar to 15.6% and similar to 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.
Eating disorders in childhood and adolescence are considered to involve both somatic and psychological problems. Treatment soon after diagnosis is aimed at correcting the nutritional and somatic ...status, including psychoeducative guidance and support for the patients and their family. Multi-professional cooperation is needed in the diagnosis and treatment of eating disorders. Once serious undernutrition is corrected, psychotherapy is indicated. Early and active treatment is associated with favourable prognosis.
Current Care Guideline: Eating disorders Suokas, Jaana; Alenius, Heidi; Ebeling, Hanna ...
Duodecim (Helsinki, Finland : 1961),
2015, Letnik:
131, Številka:
12
Magazine Article
Early diagnosis with intervention is linked to better outcome. In primary care patients in risk for eating disorder should be screened and actively asked about eating disorder symptoms. Treatment is ...mainly out-patient care and should first be focused on gaining a normal nutritional status. It is important to involve the patient's family in the treatment. A confidential relationship between health care professionals and the patient is important. The patient's own motivation and readiness for recuperation are essential. Different therapeutic and psychosocial approaches are central in the treatment, as the disorders are psychiatric. Medical treatment may bring additional help in treating binge-eating disorder or bulimia nervosa, but it is seldom of help in treating anorexia nervosa.
