1.
Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.
Spracklen, CN, Karaderi, T, Yaghootkar, H, Schurmann, C, Fine, RS, Kutalik, Z, Preuss, MH, Lu, Y, Wittemans, LBL, Adair, LS, et al
American journal of human genetics. 2019;(1):15-28
Abstract
Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
2.
Adiponectin, Insulin Sensitivity and Diabetic Retinopathy in Latinos With Type 2 Diabetes.
Kuo, JZ, Guo, X, Klein, R, Klein, BE, Genter, P, Roll, K, Hai, Y, Goodarzi, MO, Rotter, JI, Chen, YD, et al
The Journal of clinical endocrinology and metabolism. 2015;(9):3348-55
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Abstract
CONTEXT AND OBJECTIVE Insulin resistance and chronic inflammation are key elements in the pathogenesis of type 2 diabetes. We hypothesized that similar mechanisms could have a role in the development of diabetic retinopathy (DR), an important microvascular complication in Latinos with type 2 diabetes. DESIGN AND SETTING A cross-sectional, family-based, observational cohort study. PATIENTS Latino subjects with type 2 diabetes (n = 507), ascertained in families via a proband with known diabetes duration of 10 years or more and/or with DR, were included. MAIN OUTCOME MEASURES Serum adiponectin was measured and insulin sensitivity was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). DR was assessed by seven-field digital fundus photography and graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Scale (range of severity levels, 10-85). RESULTS Fasting adiponectin concentrations were elevated in patients with DR compared to those without (12.9 ± 0.5 vs 10.5 ± 0.5 μg/mL; P = .0004) and remained significant after adjusting for multiple covariates (age, gender, body mass index, glycosylated hemoglobin, diabetes duration, statin use, blood pressure, and renal function; P = .013 to .018). Adiponectin was also positively correlated with severity of DR in patients with nonproliferative DR (P < .0003), significant also after all covariate adjustments (P = .018). When the proliferative DR group was included, this relationship was attenuated by adjustments, possibly an influence of estimated glomerular filtration rate reduction in the proliferative DR group. HOMA-IR was not different in the DR and non-DR groups. Although elevated, adiponectin retained a typical inverse relationship with HOMA-IR in DR, similar to that seen in the non-DR group. CONCLUSIONS Serum adiponectin is elevated in DR, is positively correlated with DR severity in Latinos with type 2 diabetes, and maintains a relationship to insulin sensitivity. Adiponectin, whether as a marker or biological mediator, may play an important role in DR, which appears to be independent of its relationship to insulin sensitivity.