Single Nucleotide Polymorphisms of the Sirtuin 1 (SIRT1) Gene are Associated With age-Related Macular Degeneration in Chinese Han Individuals

Abstract

To investigate whether 3 variants in sirtuin 1 (SIRT1) gene contributed differently in patients with age-related macular degeneration (AMD) in a Chinese Han population.We conducted a case–control study in a group of Chinese patients with AMD (n = 253) and contrasted the results against a control group (n = 292). Three single nucleotide polymorphisms (SNPs) of SIRT1 gene including rs12778366, rs3740051, and rs4746720 were genotyped using improved multiplex ligase detection reaction. The association between targeted SNPs and AMD was then analyzed by codominant, dominant, recessive, and allelic models.The genotyping data of rs12778366, rs3740051, and rs4746720 revealed significant deviations from Hardy–Weinberg equilibrium tests in the AMD group but not in the control group.We detected significantly differences of rs12778366 allele distribution between 2 groups in recessive and codominant model (P < 0.05). Homozygous carriers of the risk allele C displayed a higher chance of developing AMD (P = 0.036, odds ratio = 3.227; 95% confidence interval: 1.015–10.265).Our study, for the first time, raises the possibility that genetic variations of SIRT1 could be implicated in the pathophysiology of AMD in the Chinese Han population.

SIRT1 Alleviates LPS-Induced IL-1β Production by Suppressing NLRP3 Inflammasome Activation and ROS Production in Trophoblasts

“…Therefore, further studies are needed to Although SIRT1 is expressed in all trophoblast layers of the placenta and is important for proper trophoblast differentiation and placental development [43], the relationship between LPS-associated placental inflammation and SIRT1 expression has not been studied previously. Recent studies showed that single nucleotide polymorphisms (SNPs) in the SIRT1 gene are associated with carotid atherosclerosis, major depressive disorder, age-related macular degeneration, and severe obesity [44][45][46][47]. However, it is not known whether SNPs in the SIRT1 gene have an influence on the NLRP3 inflammasome-mediated inflammatory diseases.…”

Role of Sirtuin 1 in the pathogenesis of ocular disease (Review)

“…The pathophysiology and risk factors of AMd are complex (40). chen et al (41) investigated three variants of the SIRT1 gene associated with AMd in chinese Han individuals, and identified that the rs12778366 polymorphism within the promoter region of SIRT1 was significantly associated with AMd in recessive and codominant models. Expression of SIRT1 was more frequent in RPE and vascular endothelial cells (VEcs) in human cNV membranes (42).…”

Advances in Age-related Macular Degeneration Understanding and Therapy

“…However, one study suggested that genetic variations of SIRT1 could be implicated in the pathophysiology of AMD in the Chinese Han population. 115 Another study indicated that lower expressions of SIRT1 and PGC1α were observed in iPSC-derived RPE cells from patients with AMD. 116 Even less data exist for AMPK and AMD—a few reports suggested AMPK and mechanistic target of rapamycin (mTOR) as potential therapeutic targets in AMD, 117 , 118 while in vitro experiments suggested a protective effect for AMPK activation on RPE cells and downregulation of complement factor B (unpublished data, Eun Jee Chung et al).…”