AHSG gene variant is associated with leanness among Swedish men

Lavebratt, Catharina; Wahlqvist, Sofia; Nordfors, Louise; Hoffstedt, Johan; Arner, Peter

doi:10.1007/s00439-005-1286-z

Cited by 45 publications

(57 citation statements)

References 35 publications

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“…45 However, obesity, which is by itself an inflammatory condition, confounded these observations. 46,47 Although AHSG can slightly modulate body mass, 48 the low serum level of this protein was independently associated with an increased risk of preeclampsia in our study. Nevertheless, the large overlap in serum AHSG and CRP levels between preeclamptic patients and healthy pregnant womenreflected also by sensitivity and specificity values-suggests that mechanisms other than systemic inflammation are also involved in the pathogenesis of this multifactorial disorder.…”

Section: Discussioncontrasting

confidence: 44%

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

et al. 2009

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The purpose of this study was to determine serum a 2 -HS glycoprotein (AHSG) concentration and its diagnostic accuracy in preeclampsia. In this case-control study, the serum C-reactive protein (CRP) and AHSG levels were measured in 93 preeclamptic patients and in 127 healthy pregnant women by immunoturbidimetry and radial immunodiffusion. The serum CRP levels were significantly higher, whereas the serum AHSG concentrations were significantly lower in the preeclamptic group than in the control group (median (25th to 75th percentile), CRP: 6.71 mg l À1 (2.76-12.69) vs. 3.38 mg l À1 (1.69-7.27), respectively; AHSG: 660 lg ml À1 (612-768) vs. 744 lg ml À1 (660-816), respectively; Po0.001 for both). In preeclamptic patients, the serum AHSG concentrations showed significant inverse correlations with systolic blood pressure and serum CRP levels. A low serum AHSG level (p720 lg ml À1 ) was significantly associated with preeclampsia (adjusted odds ratio (95% confidence interval): 3.69 (1.82-7.51); Po0.001). According to the receiver operating characteristic curves, the measurement of serum AHSG concentrations was as accurate as that of serum CRP levels to detect preeclampsia. In conclusion, serum AHSG concentration is decreased and reflects-at least partly-systemic inflammation in preeclampsia.

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Section: Discussioncontrasting

confidence: 44%

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

et al. 2009

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“…Thr248Met and Thr256Ser (rs4918), which are in almost perfect linkage disequilibrium (LD), were examined among 176 Japanese subjects in relation to serum concentrations of AHSG, which proved to be largely dependent on AHSG Thr248Met and Thr256Ser genotypes (13). Both of these single nucleotide polymorphisms (SNPs) are in almost perfect LD with a third variant, IVS1-903AϾG (rs2593813), which was associated with overweight/obesity among 504 Swedish men, alone and in a haplotype combination with Thr248Met and Thr256Ser (14). In a French study (15) involving 1,655 participants, AHSG was resequenced and frequent SNPs (minor allele frequencies [MAFs] Ͼ5%) were investigated for association with type 2 diabetes.…”

Section: Research Design and Methods-mentioning

confidence: 99%

“…Also, logistic regression with adjustment for age, sex, and BMI (where appropriate) was applied assuming an additive model. Power calculations were performed assuming ORs of 1.27 and 1.74, as observed in previous reports (14,15), a significance level of 95%, and a sample size of 1,005, which was the smallest number of subjects entering any analysis. A general linear model was used to test quantitative variables for differences between genotype groups among glucose-tolerant subjects not receiving any medication (glucose tolerance status is determined according to 19), and the P values describe an additive model.…”

Section: Methodsmentioning

confidence: 99%

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

et al. 2008

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OBJECTIVE-The gene encoding the ␣2 Heremans-Schmid glycoprotein (AHSG) is a credible biological and positional candidate gene for type 2 diabetes and the metabolic syndrome, and previous attempts to relate AHSG variation with type 2 diabetes and obesity in Swedish and French Caucasians have been largely successful. We related seven frequent AHSG tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia. RESEARCH DESIGN AND METHODS-The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, providing a statistical power of Ͼ99% to replicate previous findings. Data were analyzed in case-control and haplotype settings, and quantitative metabolic traits were examined for association. Moreover, epistatic effects between AHSG variants and insulin receptor substrate-1 (IRS1) and ␤-2-adrenergic receptor polymorphisms were investigated.RESULTS-The Ϫ469TϾG (rs2077119) and IVS6ϩ98CϾT (rs2518136) polymorphisms were associated with type 2 diabetes (P ϭ 0.007 and P ϭ 0.006, respectively, or P corr ϭ 0.04 and P corr ϭ 0.03, respectively, following correction for multiple hypothesis testing), and in a combined analysis of the present and a previous study Ϫ469TϾG remained significant (odds ratio 0.90 [95% CI 0.84 -0.97]; P ϭ 0.007). Furthermore, two AHSG haplotypes were associated with dyslipidemia (P ϭ 0.003 and P corr ϭ 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-oral glucose tolerance test serum insulin release (P ϭ 0.02, P corr ϭ 0.1 for fasting and P ϭ 0.04, P corr ϭ 0.2 for area under the insulin curve) and improved insulin sensitivity estimated by the homeostasis model assessment of insulin resistance (9.0 vs. 8.6 mmol ⅐ l Ϫ1 ⅐ pmol Ϫ1 ⅐ l Ϫ1 ; P ϭ 0.01, P corr ϭ 0.06). Indications of epistatic effects of AHSG variants with the IRS1 Gly971Arg polymorphism were observed for fasting serum triglyceride concentrations.CONCLUSIONS-Based on present and previous findings, common variation in AHSG may contribute to the interindividual variation in metabolic traits. Diabetes 57:1427-1432, 2008 T he ␣ 2 Heremans-Schmid glycoprotein (AHSG) is secreted mainly by the liver and is abundant in plasma. AHSG inhibits insulin-stimulated insulin receptor autophosphorylation, insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS1), and the association of IRS1 with the p85 subunit of phosphatidylinositol-3 kinase in vitro (1-3). Elevated plasma AHSG was associated with insulin resistance in humans (4), and AHSG levels were higher in subjects with impaired glucose tolerance (5) and women with gestational diabetes (6). Ahsg knockout mice demonstrate increased basal and insulin-stimulated insulin receptor phosphorylation, increased glucose clearance, and insulin sensitivity (7). Moreover, even on a high-fat diet and at old age Ahsg knockout mice were resistant to weight gain and remained insulin sens...

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“…Increased fat mass may also have direct pathophysiological effects on the kidney; through glomerular hyperfiltration, growth factors and adipokine alterations may lead to fibrosis, glomerulosclerosis, and kidney disease. *A study by Lavebratt et al 113 shows that a common variant of a-HeremansSchmid glycoprotein (AHSG) associated with lower fetuin levels is more common in lean than obese patients. Thus, it could be hypothesized that this genetic trait may protect obese dialysis patients from mineral stress and progressing vascular calcification by a genetic predisposition to higher systemic levels of fetuin-A.…”

Section: Mechanisms Of Obesity: Why Do We Get Fat?mentioning

confidence: 99%

Obesity in CKD—What Should Nephrologists Know?

Stenvinkel

Zoccali

İkizler

2013

Journal of the American Society of Nephrology

193

172

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Obesity, the epidemic of the 21st century, carries a markedly increased risk for comorbid complications, such as type 2 diabetes, cancer, hypertension, dyslipidemia, cardiovascular disease, and sleep apnea. In addition, obesity increases the risk for CKD and its progression to ESRD. Paradoxically, even morbid obesity associates with better outcomes in studies of ESRD patients on maintenance dialysis. Because the number of obese CKD and maintenance dialysis patients is projected to increase markedly in developed as well as low-and middle-income countries, obesity is a rapidly emerging problem for the international renal community. Targeting the obesity epidemic represents an unprecedented opportunity for health officials to ameliorate the current worldwide increase in CKD prevalence. Nephrologists need more information about assessing and managing obesity in the setting of CKD. Specifically, more precise estimation of regional fat distribution and the amount of muscle mass should be introduced into regular clinical practice to complement more commonly used practical markers, such as body mass index. Studies examining the effects of obesity on kidney disease progression and other clinical outcomes along with weight management strategies are much needed in this orphan area of research. 24: 172724: -173624: , 201324: . doi: 10.1681 Obesity has emerged as the largest pandemic in near history, with important implications of not only cardiovascular disease (CVD) but also CKD. Recent data from the United States indicate that the incidence and prevalence rates of obesity in maintenance dialysis patients largely exceed the corresponding figures in the general population. 1 A large European population survey documented that a high body mass index (BMI) ranks as one of the strongest risk factors for new-onset CKD. 2 The dimension of the obesity epidemic and the impact of the same epidemic on the kidney demand efforts for understanding the epidemiology and the mechanisms of CKD associated with excess adiposity. It also sets as an absolute public health priority for the development of treatment policies integrated across specialties and general practice to halt this much concerning problem. In this scenario, it is fundamental that nephrologists are updated on current knowledge about obesity in the setting of CKD. However, little attention is still paid to this issue in major nephrology journals. The suboptimal attention to the problem by major sources of dissemination of specialty information suggests that nephrologists may have scarce knowledge of how obesity should be assessed, its epidemiology, mechanisms whereby excess fat mass is conducive to CKD, and management of obesity in the catabolic uremic milieu. 3 J Am Soc Nephrol DEFINITION AND ASSESSMENT OF OBESITYThe most common method for defining obesity is based on BMI (i.e., a person's weight as obese. It should be emphasized that population norms of BMI could be different based on ethnic and racial background (i.e., the proportion of Asian people with a high ...

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AHSG gene variant is associated with leanness among Swedish men

Cited by 45 publications

References 35 publications

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

Obesity in CKD—What Should Nephrologists Know?

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