LIPC rs10468017, rs493258 and LPL rs12678919 Role in Patients With Age- Related Macular Degeneration

Abstract

Objective: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly individuals in developed countries. The etiology and pathophysiology of AMD are not fully understood. Formation of drusen is the main pathological change in AMD. Lipids make up about 40% of drusen volume, thus possible relation between AMD and genes controlling lipid metabolism could provide novel insights into AMD. Our purpose was to determine the genotype frequencies of LIPC rs10468017, rs493258 and LPL rs126789919 in patients with AMD in Lithuanian population. Methods:The study enrolled 279 patients with early AMD, 256 patients with exudative AMD, and 829 healthy controls (reference group). The genotyping was carried out using the RT-PCR.Results: LIPC rs10468017 polymorphism was associated with a decreased risk of early and exudative AMD, while LPL rs126789919 polymorphism was associated with a decreased risk of exudative AMD and LIPC rs493258 was only associated with a decreased risk of early AMD. Conclusion:The study showed that LIPC rs10468017, rs493258 and LPL rs126789919 gene polymorphisms may have a protective role in AMD development.Keywords: Age-related macular degeneration; LIPC rs10468017; LIPC rs493258; LPL rs126789919; Gene polymorphism; Early AMD; Exudative AMD; Lipid metabolism IntroductionAge-related macular degeneration (AMD) is a degenerative disease affecting central part of the retina (macula). Half of the blindness cases in industrialized countries are AMD related [1]. This disease affects 2.5 million persons in Europe, and 1.75 million in the USA [2,3]. About 13.8% of population in Lithuania is also affected by AMD. AMD is a complex disease with many contributing factors: age, oxidative stress, inflammatory processes, genetic factors and others as well as their interrelationship [4].Aging process causes changes in human retina such as the appearance of drusen, an ophthalmoscopically visible focal yellow deposition of acellular polymorphous debris between the retinal pigment epithelium and Bruch's membrane [5]. In early AMD, a large number (≤ 10) of drusen result in diffuse regions with hyperpigmentation or hypopigmentation [6,7]. Late form of AMD is classified into dry (geographic atrophy of the retinal pigment epithelium with the lack of neovascularization areas) and wet type (or exudative; new blood vessel formations in choroid, called the choroidal neovascularization areas, further leading to the formation of the disciform scars) [6]. The wet form of AMD causes more severe damage to the retina and more frequently leads to devastating consequences, such as vision loss, than the dry form of AMD [6,7].In drusen lipids represent at least 40% of the volume [8]. Thus, lipid metabolism and particularly high-density lipoprotein may be involved in the pathogenic mechanism of AMD [8]. Lipid particles accumulate within Bruch's membrane prior to the development of basal deposits or drusen. This observation has led to the hypothesis that these lipid particles contribute to drusen formation dur...