Genetic polymorphisms of the SHBG gene can be the effect on SHBG and HDL-cholesterol levels in Coronary Heart Disease: a case–control study

Kurnaz-Gomleksiz, Ozlem; Akadam-Teker, Başak; Buğra, Zehra; Ömer, Beyhan; Yilmaz-Aydogan, Hülya

doi:10.1007/s11033-019-04880-x

Cited by 4 publications

(6 citation statements)

References 56 publications

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“…HDL‐C increased by approximately 25% 2 years after surgery, an increase that was maintained throughout the 12‐year follow‐up period despite weight regain and that was larger than any other clinical change (3). HDL‐C has a strong positive association with SHBG even after adjusting for multiple cardiovascular risk factors (35). Polymorphisms in the SHBG gene have been associated with abundance of the SHBG protein, HDL‐C, diabetes, and CHD (35‐37).…”

Section: Discussionmentioning

confidence: 99%

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Proteome‐wide associations with short‐ and long‐term weight loss and regain after Roux‐en‐Y gastric bypass surgery

Yousri

Engelke

Sarwath

et al. 2021

Obesity

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Objective Gastric bypass surgery results in long‐term weight loss. Small studies have examined protein changes during rapid weight loss (up to 1 or 2 years post surgery). This study tested whether short‐term changes were maintained after 12 years. Methods A 12‐year follow‐up, protein‐wide association study of 1,297 SomaLogic aptamer‐based plasma proteins compared short‐ (2‐year) and long‐term (12‐year) protein changes in 234 individuals who had gastric bypass surgery with 144 nonintervened individuals with severe obesity. Results There were 51 replicated 12‐year protein changes that differed between the surgery and nonsurgery groups. Adjusting for change in BMI, only 12 proteins remained significant, suggesting that BMI change was the primary reason for most protein changes and not non‐BMI‐related surgical effects. Protein changes were related to BMI changes during both weight‐loss and weight‐regain periods. The significant proteins were associated primarily with lipid, uric acid, or resting energy expenditure clinical variables and metabolic pathways. Eight protein changes were associated with 12‐year diabetes remission, including apolipoprotein M, sex hormone binding globulin, and adiponectin (p < 3.5 × 10−5). Conclusions This study showed that most short‐term postsurgical changes in proteins were maintained at 12 years. Systemic protection pathways, including inflammation, complement, lipid, and adipocyte pathways, were related to the long‐term benefits of gastric bypass surgery.

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Section: Discussionmentioning

confidence: 99%

“…HDL‐C has a strong positive association with SHBG even after adjusting for multiple cardiovascular risk factors (35). Polymorphisms in the SHBG gene have been associated with abundance of the SHBG protein, HDL‐C, diabetes, and CHD (35‐37). SHBG was tightly clustered with IGFBP2, suggesting additional effects beyond HDL‐C (31).…”

Section: Discussionmentioning

confidence: 99%

Proteome‐wide associations with short‐ and long‐term weight loss and regain after Roux‐en‐Y gastric bypass surgery

Yousri

Engelke

Sarwath

et al. 2021

Obesity

View full text Add to dashboard Cite

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“…HDL-C increased by approximately 25% two years after surgery, which increase was maintained throughout the 12-year follow-up period despite weight regain and was larger than any other clinical change 4 . HDL-C has a strong positive association with SHBG even after adjusting for multiple cardiovascular risk factors 33 . Polymorphisms in the SHBG gene have been associated with abundance of the SHBG protein, HDL-C, diabetes, and CHD 33-35 .…”

Section: Discussionmentioning

confidence: 99%

“…HDL-C has a strong positive association with SHBG even after adjusting for multiple cardiovascular risk factors 33 . Polymorphisms in the SHBG gene have been associated with abundance of the SHBG protein, HDL-C, diabetes, and CHD 33-35 . Additionally, decreases in AFM, APOE (associated with decreased TG), and increases in ADIPOQ and APOM (associated with increased HDL-C) after surgery suggest these proteins may be responsible for the sustained large increase in HDL-C.…”

Section: Discussionmentioning

confidence: 99%

Twelve-year changes in protein profiles in patients with and without gastric bypass surgery

Yousri

Engelke

Sarwath

et al. 2020

Preprint

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Gastric bypass surgery results in long-term weight loss due to re-routing of the gastro-intestinal anatomy and dietary intake alterations. Studies have examined protein change during rapid weight loss (up to 1 year post-surgery), but whether protein changes are maintained long-term after weight stabilization is unknown. To identify proteins and pathways involved with the long-term beneficial effects of weight loss, abundances of 1297 blood-circulating proteins were measured at baseline, 2 and 12 years after Roux-en-Y gastric bypass surgery. Protein changes were compared between 234 surgery and 144 non-surgery subjects with severe obesity, with discovery and replication subgroups. Seventy-one protein changes were associated with 12-year BMI changes and 58 (7 unique) with surgical status. Protein changes, including ApoM, were most strongly associated with long-term changes in lipids (HDL-C and triglycerides). Inflammation, adipogenesis, cellular signaling, and complement pathways were implicated. Short-term improvements in protein levels were maintained long-term, even after some weight regain.

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“…related with metabolic effects in case-control studies. Low levels of SHBG were correlated with cardiac risk since HDL-L levels were lower than the normal threshold in patients with coronary heart disease, and this correlation might be affected by SHBG polymorphism [130]. Carriers of the SHBG polymorphisms rs6257 and rs6259 present a higher risk of diabetes than carriers of other alleles and present low levels of SHBG [131].…”

Section: Human Diseases and Medications Related Tomentioning

confidence: 99%

Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

Basualto-Alarcón

García‐Rivas

Troncoso

et al. 2021

International Journal of Endocrinology

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In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

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Genetic polymorphisms of the SHBG gene can be the effect on SHBG and HDL-cholesterol levels in Coronary Heart Disease: a case–control study

Cited by 4 publications

References 56 publications

Proteome‐wide associations with short‐ and long‐term weight loss and regain after Roux‐en‐Y gastric bypass surgery

Proteome‐wide associations with short‐ and long‐term weight loss and regain after Roux‐en‐Y gastric bypass surgery

Twelve-year changes in protein profiles in patients with and without gastric bypass surgery

Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

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