Molecular genetics of microvascular disease in diabetic retinopathy

Warpeha, Katherine M.; Chakravarthy, Usha

doi:10.1038/sj.eye.6700348

Cited by 84 publications

(55 citation statements)

References 68 publications

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“…Candidate gene studies have, for the most part, reported conflicting results (12), and there have been few genomewide studies. Our group previously conducted genomewide linkage analysis for retinopathy in diabetic Pima Indians who had participated in a linkage study designed to identify loci for diabetes and obesity (13,14).…”

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confidence: 99%

Genome-Wide Linkage Analyses to Identify Loci for Diabetic Retinopathy

et al. 2007

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Hyperglycemia and long duration of diabetes are widely recognized risk factors for diabetic retinopathy, but inherited susceptibility may also play a role because retinopathy aggregates in families. A genome-wide linkage analysis was conducted in 211 sibships in which >2 siblings had diabetes and retinal photographs were available from a longitudinal study. These sibships were a subset of 322 sibships who had participated in a previous linkage study of diabetes and related traits; they comprised 607 diabetic individuals in 725 sibpairs. Retinal photographs were graded for presence and severity of diabetic retinopathy according to a modification of the Airlie House classification system. The grade for the worse eye was adjusted for age, sex, and diabetes duration and analyzed as a quantitative trait. Heritability of diabetic retinopathy in this group was 18% (95% CI 2-36). A genome-wide linkage analysis using variance components modeling found evidence of linkage on chromosome 1p. Using single-point analysis, the peak logarithm of odds (LOD) was 3.1 for marker D1S3669 (34.2 cM), whereas with multipoint analysis the peak LOD was 2.58 at 35 cM. No other areas of suggestive linkage were found. We propose that an area on chromosome 1 may harbor a gene or genes conferring susceptibility to diabetic retinopathy.

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confidence: 99%

Genome-Wide Linkage Analyses to Identify Loci for Diabetic Retinopathy

et al. 2007

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“…Furthermore, sub-group analysis in the Diabetes Control and Complications Trial showed strong familial transmission for DR, especially in patients with severe proliferative retinopathy (The Diabetes Control and Complications Trial Research Group 1997). These facts represent convincing evidence that genetic factors contribute to the development of DR, but the genes conferring susceptibility remain to be identified (Simonelli et al 2001;Warpeha and Chakravarthy 2003).…”

Section: Introductionmentioning

confidence: 87%

The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis

et al. 2005

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The association between retinopathy in type 2 diabetes [diabetic retinopathy (DR)] and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in several case-control studies. These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of developing DR whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DR was conducted. Four out of five identified studies included populations of East Asian descent, and only one involved samples from European descent (Caucasians). Overall, the meta-analysis suggested large heterogeneity between studies (p = 0.08, I 2 = 52%) and marginal association between C677T transition and the risk of developing DR: random effects odds ratio (OR) = 1. There is a source of bias in the selected studies: the largest studies failed to show association while the smallest study claimed an association. The above findings reinforce the need for larger and more rigourous studies in this area.

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“…As a consequence, a sudden burst of NO synthesis occurs leading to severe vasodilation and circulatory collapse. In diabetic milieu as long as NOS3 expression is low, the induction of NOS2 expression may occur in an attempt to achieve homeostasis, being crucial in preventing or delaying pathological alterations in the microcirculation (Warpeha & Chakravarthy 2003). In studies of diabetic complications, as DR and DN, influenced by vascular functional disturbances, the increased NO formation via NOS2 expression has been reported (Johannesen et al, 2000a).…”

Section: Nos2a Genementioning

confidence: 99%

“…Assessement of polymorphisms in T1DM for the prevalence of DR showed that the 14-repeat allele of (CCTTT)n repeat polymorphism in NOS2A was significantly associated with the absence of the disease. A person with diabetes carrying this allele has 0.21-fold chance of developing retinopathy as compared to those not carrying the allele, suggesting that the carriage of the 14-repeat allele is not a feature of diabetes itself, but is specific to DR development (Warpeha et al, 1999;Warpeha & Chakravarthy, 2003). In addition, the same NOS2A variant, the 14-repeat allele, was found to represent a low risk for DN (Johannesen et al, 2000b), and other report indicated that carriers of this allele have the low risk of DPN in T1DM (Nosikov, 2004;Zotova et al, 2005).…”

Section: Nos2a Genementioning

confidence: 99%

“…In a previous review was shown that EDN1 gene was directly involved in hypertension and polymorphisms in EDNRA were associated with essential hypertension testifying the necessity of a balance within the endothelin system for normal functioning in vascular tissues. Although the importance of ET-1 expression in retinal microvasculature in high glucose was incontrovertible, it appears to be a lack of association between EDN1 and ECE1 polymorphisms and DR (Warpeha & Chakravarthy, 2003). Interestigly, in T2DM the TT genotype of EDN1 G/T polymorphism was associated with reduce risk of DN (Li et al, 2008).…”

Section: Endothelin Genesmentioning

confidence: 99%

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