ABSTRACT
PURPOSE: Polymorphisms of the engulfment and cell motility 1 (ELMO1) gene were recently associated with type 2 diabetes (T2DM) and its complications. We investigated the association of rs10255208, rs7782979, and rs2041801 ELMO1 gene variants with T2DM in Tunisian Arabs. METHODS: Subjects comprised 900 T2DM patients and 600 normoglycemic controls. ELMO1 genotyping was done by PCR-RFLP; the contribution of ELMO1 variants to T2DM was analyzed by Haploview and regression analysis. RESULTS: Minor allele frequencies of rs7782979 and rs10255208 ELMO1 variants were significantly higher among unselected T2DM cases than controls, and significant differences in the distribution of rs7782979 genotypes were seen between T2DM cases and control subjects, which was seen in male but not female subjects. Three-locus ELMO1 haplotype analysis identified haplotype GAA to be positively associated, and haplotypes GCA, AAA, and GCG to be negatively associated with T2DM. The distribution of these haplotypes was gender-dependent for some (GCA, GCG, AAG), and gender-independent for others (GAA, AAA). This translated into altered risk of T2DM in male or female subjects, which persisted after adjusting for BMI, systolic and diastolic blood pressure, and serum lipid profile. CONCLUSION: These results confirm role for ELMO1 as T2DM susceptibility locus, which appears to be gender-dependent.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Arabs/genetics , Biomarkers/analysis , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Female , Follow-Up Studies , Gene Frequency , Genotype , Haplotypes/genetics , Humans , Male , Middle Aged , Prognosis , Sex Factors , Tunisia/epidemiologyABSTRACT
The use of elderly deceased donors requires refining criteria for both the donor and the recipient. This report attempted to identify parameters susceptible to further improvement. This retrospective multicenter study analyzed the outcomes of kidney recipients from 15 consecutive elderly deceased donors in the south French region (IR9). Donors were 65 to 74 years old. Mean creatinine clearance was 80 mL/min/1.73 m(2). The donor risk factors for allograft dysfunction were stroke, hypertension, cardiovascular disease, cardiac death, smoking, arrhythmia, and diabetes. The recipients were 35 to 70 years old. The median cold ischemia time was 24 hours. Four patients (16%) suffered delayed graft function (DGF). Three recipients (12%) died within the first 2 months after transplantation. The postoperative complications (29%) were 2 renal artery thromboses, 4 renal artery stenoses, and 1 toe ischemia. Two years after transplantation, their mean serum creatinine was 157 micromol/L. The patient and graft survivals were 88% and 70%, respectively. These results seemed worse than those reported in the literature, but it was a small cohort and a new experience. DGF is probably linked to improvable management to reduce cold ischemia time. The elevated rate of surgical complications might be related to a lack of experience in donor and recipient evaluations. Kidney transplantation from elderly donors requires an efficient organization and an accurate evaluation of both donor renal function and recipient cardiovascular state.
Subject(s)
Kidney Transplantation/physiology , Tissue Donors/statistics & numerical data , Aged , Cadaver , Cause of Death , Creatinine/blood , Female , Follow-Up Studies , Humans , Male , Medical History Taking , Patient Selection , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Non-Shiga toxin-associated hemolytic uremic syndrome (non-Stx-HUS) is a rare disease. The clinical outcome is often unfavorable: 50% of patients progress to end-stage renal failure. Several mutations in complement regulatory genes predispose to non-Stx-HUS. Transplantation outcomes are poor among patients with either mutation in the genes encoding complement H or I factors, with 80% graft loss due to HUS recurrence. In contrast, patients with mutation in the gene encoding MCP have no disease relapse after transplantation. There are no treatment guidelines for non-Stx-HUS recurrence. Herein we have presented 8 patients with non-Stx-HUS recurrence after transplantation during the last 10 years in the South of France. HUS recurrence, which occurred early after transplantation in all but 1 patient, was treated by plasma exchange (PE) with substitution by fresh frozen plasma (FFP). Three patients still treated with long-term plasma therapy have no recurrence at 15, 19, or 24 months. An international registry would help to define new guidelines.
