ABSTRACT Objective: To investigate the association of the rs741301 polymorphism in the ELMO1 gene with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Materials and methods: This study analyzed 350 patients with T2DM and DR (cases) and 234 patients with T2DM without this complication but with more than 10 years of diabetes mellitus (DM) (controls). DR was diagnosed by indirect fundoscopy. Genotyping was performed by allelic discrimination real-time PCR. Results: The frequency of the C/C genotype of the rs741301 polymorphism in the ELMO1 gene was 26.9% in cases and 17.9% in controls (P = 0.011). After adjustment for covariables, the C/C genotype was associated with an increased risk of DR [odds ratio (OR) = 1.805, 95%CI 1.101–2.961; P = 0.019]. This association remained significant in dominant and additive inheritance models after adjustment for the same variables [OR = 1.597, 95%CI 1.089-2.343; P = 0.017; and OR = 1.818, 95%CI 1.099-3.007; P = 0.020]. Conclusion: This study demonstrated an association between the presence of the C allele of the ELMO1 rs741301 polymorphism and an increased risk of DR in patients with T2DM from Southern Brazil. Objective rs rs74130 ELMO (DR T2DM. TDM . T DM (T2DM) methods 35 (cases 23 1 (DM controls. (controls) fundoscopy realtime real time PCR Results CC 269 26 9 26.9 179 17 17.9 0.011. 0011 0.011 0 011 0.011) covariables odds (OR 1805 805 1.805 95CI CI 95 1.101–2.961 11012961 101 961 0.019. 0019 0.019 019 0.019] 1597 597 1.597 1.0892.343 10892343 1.089 2.343 089 343 1.089-2.343 0.017 0017 017 1818 818 1.818 1.0993.007 10993007 1.099 3.007 099 3 007 1.099-3.007 0.020. 0020 0.020 020 0.020] Conclusion Brazil rs7413 (T2DM (controls 26. 17. 001 0.01 01 180 80 1.80 1.101–2.96 1101296 96 159 59 1.59 0892 1.0892.34 1089234 1089 1.08 2343 2.34 08 34 1.089-2.34 181 81 1.81 0993 1.0993.00 1099300 1099 1.09 3007 3.00 09 00 1.099-3.00 002 0.02 02 rs741 0.0 18 8 1.8 1.101–2.9 110129 15 5 1.5 1.0892.3 108923 108 1.0 2.3 1.089-2.3 1.0993.0 109930 109 300 3.0 1.099-3.0 rs74 0. 1. 1.101–2. 11012 1.0892. 10892 2. 1.089-2. 1.0993. 10993 30 3. 1.099-3. rs7 1.101–2 1101 1.0892 1.089-2 1.0993 1.099-3 1.101– 110 1.089- 1.099- 1.101 11 1.10 1.1

ABSTRACT Objective: To investigate the association between the long noncoding RNAs (lncRNAs) maternally expressed gene 3 (MEG3) rs7158663 polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Subjects and methods: The study included 628 patients with T2DM and DR ("case group," including 283 with proliferative DR [PDR] and 345 with nonproliferative DR [NPDR]), and 381 patients with T2DM but no DR ("control group"). The diagnosis of DR was established using indirect ophthalmoscopy. The rs7158663 A/G polymorphism was genotyped using real-time polymerase chain reaction (PCR) with TaqMan probes. Results: Patients with DR, compared with those without DR, had lower frequencies of both the G/G genotype (17.5% and 23.6%, respectively, p = 0.044) and the G allele (p = 0.017). When only patients with PDR were compared with controls, the G/G genotype was associated with increased protection against PDR after adjustment (odds ratio 0.551, 95% confidence interval 0.314–0.966, p = 0.038). This association also remained in the dominant (p = 0.036) and additive (p = 0.031) genetic models. Conclusion: This study reveals, for the first time, that the G/G genotype of the lncRNA MEG3 rs7158663 single-nucleotide polymorphism is associated with a protective effect against advanced-stage DR in patients with T2DM. Additional studies are warranted to validate this finding. Objective lncRNAs (lncRNAs MEG (MEG3 rs rs715866 (DR TDM . T DM (T2DM) methods 62 case group, group 28 [PDR 34 NPDR, NPDR , [NPDR]) 38 control group. group") ophthalmoscopy AG A realtime real time PCR (PCR probes Results GG 17.5% 175 17 5 (17.5 236 23 6 23.6% respectively 0.044 0044 0 044 0.017. 0017 0.017 017 0.017) controls odds 0551 551 0.551 95 03140966 314 966 0.314–0.966 0.038. 0038 0.038 038 0.038) 0.036 0036 036 0.031 0031 031 models Conclusion reveals singlenucleotide single nucleotide advancedstage advanced stage finding (MEG rs71586 (T2DM [NPDR] group" 17.5 1 (17. 23.6 0.04 004 04 001 0.01 01 055 55 0.55 9 0314096 31 96 0.314–0.96 003 0.03 03 rs7158 [NPDR 17. (17 23. 0.0 00 05 0.5 031409 0.314–0.9 rs715 (1 0. 03140 0.314–0. rs71 ( 0314 0.314–0 rs7 0.314– 0.314 0.31 0.3

Abstract Long non-coding RNAs (lncRNAs) are RNAs with >200 nucleotides that are unable to encode proteins and are involved in gene expression regulation. LncRNAs have a key role in many physiological and pathological processes and, consequently, they have been associated with several human diseases, including diabetes chronic complications, such as diabetes kidney disease (DKD). In this context, some studies have identified the dysregulation of the lncRNAs MALAT1 and TUG1 in patients with DKD; nevertheless, available data are still contradictory. Thus, the objective of this study was to compare MALAT1 and TUG1 expressions in urine of patients with type 1 diabetes mellitus (T1DM) categorized according to DKD presence. This study comprised 18 T1DM patients with DKD (cases) and 9 long-duration T1DM patients without DKD (controls). MALAT1 and TUG1 were analyzed using qPCR. Bioinformatics analyses were done to identify both lncRNA target genes and the signaling pathways under their regulation. The lncRNA MALAT1 was upregulated in urine of T1DM patients with DKD vs. T1DM controls (P = 0.007). The expression of lncRNA TUG1 did not differ between groups (P = 0.815). Bioinformatics analysis showed these two lncRNAs take part in metabolism-related pathways. The present study shows that the lncRNA MALAT1 is upregulated in T1DM patients presenting DKD. noncoding non coding (lncRNAs 200 >20 regulation consequently diseases complications . (DKD) context MALAT TUG nevertheless contradictory Thus TDM T DM (T1DM presence cases (cases longduration long duration controls. (controls) qPCR vs P 0.007. 0007 0.007 0 007 0.007) 0.815. 0815 0.815 815 0.815) metabolismrelated metabolism related 20 >2 (DKD (controls 000 0.00 00 081 0.81 81 2 > 0.0 08 0.8 8 0.