Neuroscience Letters 513 (2012) 233–237 Contents lists available at SciVerse ScienceDirect Neuroscience Letters jou rn al h om epage: www.elsevier.com/locate/neulet Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population Kai Kaarniranta a,d,∗ , Jussi Paananen b , Tanja Nevalainen c , Iiris Sorri d , Sanna Seitsonen e , Ilkka Immonen e , Antero Salminen f,g , Leena Pulkkinen b , Matti Uusitupa b,h a Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland b Department of Clinical Nutrition and Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland c Department of Ophthalmology, North Karelia Central Hospital, Joensuu, Finland d Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland e Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland f Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland g Department of Neurology, Kuopio University Hospital, Kuopio, Finland h Research Unit, Kuopio University Hospital, Kuopio, Finland a r t i c l e i n f o Article history: Received 31 October 2011 Received in revised form 1 February 2012 Accepted 14 February 2012 Keywords: Adiponectin Aging Macular degeneration Polymorphism a b s t r a c t Adiponectin is an adipocyte-expressed protein that regulates the glucose, lipid, and energy metabolism via adiponectin receptors 1 and 2. Obesity is a known risk factor for age-related macular degeneration (AMD). We, therefore, examined associations of single nucleotide polymorphisms in Adiponectin (ADIPOQ) and Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) genes with the prevalence of advanced AMD in Finnish population. Thirty-seven markers for ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in a sample collection of 91 men and 177 women having exudative AMD and 18 men and 26 women having severe atrophic AMD. Patients were diagnosed by fundus photographs and fluorescein angiography. The control group (no signs of AMD in fundus photographs) consisted of 55 men and 111 women. Inclusion criteria age was over 65 years old without diabetes diagnosis. Out of the tested SNPs, rs10753929 located in intron of ADIPOR1 gene was significantly associated (p = 0.0471) with AMD status when using a permutation procedure that controlled for the number of tested genotypes and genetic models. Odds ratio (OR) for the association was 1.699 (95% CI 1.192–2.423). The SNP consists of C/T alleles and the risk allele T had a minor allele frequency (MAF) of 20.4%. Distribution of proportion of cases/controls between alleles revealed an additive genetic model. Our findings reveal that rs10753929 ADIPOR1 variant is a novel candidate for AMD genetic risk factor in Finnish population. © 2012 Elsevier Ireland Ltd. All rights reserved. Age-related macular degeneration (AMD) etiology is known to be multifactorial, i.e. in addition to a strong genetic component, environmental risk factors such as smoking, obesity, atheroscle- rosis, hypertension and hypercholesterolemia may predispose to AMD [17]. Chronic retinal oxidative stress and inflammation are strongly linked to AMD pathogenesis and progression [4,15]. Despite advances in our understanding of the pathogenesis of AMD and the treatment of its neovascular complications, there is incom- plete knowledge of environmental factors that can modify its onset and progression. Obesity presents an increasing problem for devel- oped and developing countries and is well established as one of ∗ Corresponding author at: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland and Kuopio University Hospital, P.O. BOX 1777, 70211 Kuopio, Finland. Tel.: +358 17 172485; fax: +358 17 172486. E-mail address: kai.kaarniranta@uef.fi (K. Kaarniranta). the risk factors for several age-related diseases including AMD [1,7,10,11,19–21,26,27,32,33,37]. Adiponectin, an adipokine hormone, is inversely related to both adiposity and many chronic inflammatory diseases. Adiponectin production is inhibited by a oxidative stress and inflammation [39]. Clinical observations have demonstrated the association of hypoadiponectinemia in patients with obesity [8]. Interestingly, one of the known AMD risk factors, smoking, decreases circu- lating adiponectin concentrations as well. Adiponectin mediates its cellular message via binding and activation of its specific receptors, adiponectin receptor 1 and adiponectin receptor 2 [22]. Adiponectin receptors belong to a new family of membrane receptors structurally predicted to contain seven transmembrane spanning domains, but are topologically distinct from G-protein coupled receptors. Adiponectin binds to the C-terminal extracellu- lar domain of ADIPOR, whereas the N-terminal cytoplasmic domain interacts and regulates intracellular signaling with an adaptor pro- tein, APPL1. ADIPOR1 is abundantly expressed in skeletal muscle 0304-3940/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2012.02.050