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      PPARG Polymorphisms Are Associated with Unexplained Mild Vision Loss in Patients with Type 2 Diabetes Mellitus

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          Abstract

          Objectives

          To investigate whether the presence of peroxisome proliferator-activated receptor gamma (PPARG) gene polymorphisms is associated with unexplained mild visual impairment (UMVI) in patients with type 2 diabetes mellitus (T2DM).

          Methods

          A total of 135 T2DM residents with UMVI and 133 with normal vision (NV; best-corrected visual acuity ≥ 20/25 in both eyes) were enrolled. UMVI was defined as best-corrected visual acuity (BCVA) < 20/25 and ≥ 20/63 in both eyes, with no visual impairment-causing diseases found. Four PPARG gene single-nucleotide polymorphisms (SNPs) (rs3856806, rs1801282, rs709158, and rs10865710) were assessed with the HAPLOVIEW 4.0 software to examine the statistical association of PPARG polymorphisms and UMVI in patients with T2DM.

          Results

          Four SNPs qualified the Hardy–Weinberg equilibrium ( p > 0.05). The frequency of genotype GC at SNP rs10865710 was significantly higher in the UMVI group than in the NV group ( p < 0.001; GG + GC versus CC) (OR = 8.94, 95% CI: 4.90–16.31), whereas genotype CC decreased the risk (OR = 0.07, 95% CI: 0.03–0.14). Genotype TT at SNP rs3856806 was strongly associated with UMVI ( p < 0.0001, TT + TC versus CC) (OR = 4.74, 95% CI: 2.68–8.54), whereas genotype CC appeared to be protective for UMVI (OR = 0.55, 95% CI: 0.37–0.82).

          Conclusions

          Susceptibilities of PPARG variants may lead to differences in PPARG transcription, result in early function loss of retinal photoreceptor cells, and eventually cause UMVI.

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          Most cited references35

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          The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.

          Genetic association studies are viewed as problematic and plagued by irreproducibility. Many associations have been reported for type 2 diabetes, but none have been confirmed in multiple samples and with comprehensive controls. We evaluated 16 published genetic associations to type 2 diabetes and related sub-phenotypes using a family-based design to control for population stratification, and replication samples to increase power. We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma(PPARgamma) with type 2 diabetes. By analysing over 3,000 individuals, we found a modest (1.25-fold) but significant (P=0.002) increase in diabetes risk associated with the more common proline allele (85% frequency). Moreover, our results resolve a controversy about common variation in PPARgamma. An initial study found a threefold effect, but four of five subsequent publications failed to confirm the association. All six studies are consistent with the odds ratio we describe. The data implicate inherited variation in PPARgamma in the pathogenesis of type 2 diabetes. Because the risk allele occurs at such high frequency, its modest effect translates into a large population attributable risk-influencing as much as 25% of type 2 diabetes in the general population.
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            The Organization, Promoter Analysis, and Expression of the Human PPARγ Gene

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              Risk Factors for Type 2 Diabetes Mellitus

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                Author and article information

                Contributors
                Journal
                J Ophthalmol
                J Ophthalmol
                JOPH
                Journal of Ophthalmology
                Hindawi
                2090-004X
                2090-0058
                2019
                12 December 2019
                : 2019
                : 5284867
                Affiliations
                1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China
                2Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
                3Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
                4Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), The Collaborative Innovation Center for Brain Science, Shanghai Jiaotong University, Shanghai, China
                5Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
                Author notes

                Academic Editor: Shigeru Honda

                Author information
                https://orcid.org/0000-0002-6831-7560
                Article
                10.1155/2019/5284867
                6930731
                245573e1-ab89-47f3-a7d8-2b19cd2dfbc1
                Copyright © 2019 Tao Li et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 April 2019
                : 11 November 2019
                : 20 November 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81670898
                Award ID: 81600778
                Funded by: Shanghai Shen Kang Hospital Development Center
                Award ID: SHDC12015315
                Award ID: SHDC2015644
                Funded by: Shanghai Three Year Public Health Action Program
                Award ID: GWIV-3.3
                Funded by: Shanghai High-level Oversea Training Team Program on Eye Public Health
                Award ID: GWTD2015S08
                Funded by: Shanghai Outstanding Academic Leader Program
                Award ID: 16XD1402300
                Funded by: Science and Technology Commission of Shanghai Municipality
                Award ID: 17511107901
                Funded by: Shanghai Municipal Education Commission
                Award ID: 20172022
                Categories
                Research Article

                Ophthalmology & Optometry
                Ophthalmology & Optometry

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