A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy

OBJECTIVE: Diabetic retinopathy is a sight-threatening microvascular complication of diabetes with a complex multifactorial pathogenesis. A systematic meta-analysis was undertaken to collectively assess genetic studies and determine which previously investigated polymorphisms are associated with diabetic retinopathy. RESEARCH DESIGN AND METHODS: All studies investigating the association of genetic variants with the development of diabetic retinopathy were identified in PubMed and ISI Web of Knowledge. Crude odds ratios (ORs) and 95% CIs were calculated for single nucleotide polymorphisms and microsatellite markers previously investigated in at least two published studies. RESULTS: Twenty genes and 34 variants have previously been studied in multiple cohorts. The aldose reductase (AKR1B1) gene was found to have the largest number of polymorphisms significantly associated with diabetic retinopathy. The z-2 microsatellite was found to confer risk (OR 2.33 [95% CI 1.49-3.64], P = 2 x 10(-4)) in type 1 and type 2 diabetes and z+2 to confer protection (0.58 [0.36-0.93], P = 0.02) against diabetic retinopathy in type 2 diabetes regardless of ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against diabetic retinopathy in type 1 diabetes (0.5 [0.35-0.71], P = 1.00 x 10(-4)), regardless of ethnicity. These associations were also found in the white population alone (P < 0.05). Polymorphisms in NOS3, VEGF, ITGA2, and ICAM1 are also associated with diabetic retinopathy after meta-analysis. CONCLUSIONS: Variations within the AKR1B1 gene are highly significantly associated with diabetic retinopathy development irrespective of ethnicity. Identification of genetic risk factors in diabetic retinopathy will assist in further understanding of this complex and debilitating diabetes complication

Hypersensitivity Reaction as a Harbinger of Acute Myeloid Leukemia: A Case Report and Review of the Literature

Cutaneous paraneoplastic syndromes comprise a broad spectrum of cutaneous reactions to an underlying malignancy. These dermatoses are not the result of metastatic spread to the skin, but rather a reaction to the presence of malignancy. Cutaneous paraneoplastic syndromes often precede the identification of a malignancy. We describe the case of a 79-year-old man with a six-month history of recalcitrant treatment- resistant dermatitis. A complete blood count test performed at the time of initial presentation was normal. The patient ultimately presented with erythroderma and was diagnosed with acute myeloid leukemia (AML). The evolution of the dermatitis to erythroderma coincided with the clinical presentation of AML, and was therefore considered to be a paraneoplastic syndrome. The patient decided against therapy and died seven weeks after diagnosis. Physicians should consider a cutaneous paraneoplastic syndrome when faced with dynamic recalcitrant dermatoses that are difficult to treat and decide on laboratory testing accordingly. Patients should be evaluated regularly for two to three years after initial diagnosis with a physical exam and review of systems to monitor for signs and symptoms of malignancy