ACE (I/D) polymorphism and response to treatment in coronary artery disease: a comprehensive database and meta-analysis involving study quality evaluation

<p>Abstract</p> <p>Background</p> <p>The role of angiotensin-converting enzyme (<it>ACE</it>) gene insertion/deletion (<it>I/D</it>) polymorphism in modifying the response to treatment modalities in coronary artery disease is controversial.</p> <p>Methods</p> <p>PubMed was searched and a database of 58 studies with detailed information regarding <it>ACE I/D </it>polymorphism and response to treatment in coronary artery disease was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. Heterogeneity and study quality issues were explored.</p> <p>Results</p> <p>Forty studies involved invasive treatments (coronary angioplasty or coronary artery by-pass grafting) and 18 used conservative treatment options (including anti-hypertensive drugs, lipid lowering therapy and cardiac rehabilitation procedures). Clinical outcomes were investigated by 11 studies, while 47 studies focused on surrogate endpoints. The most studied outcome was the restenosis following coronary angioplasty (34 studies). Heterogeneity among studies (p < 0.01) was revealed and the risk of restenosis following balloon angioplasty was significant under an additive model: the random effects odds ratio was 1.42 (95% confidence interval:1.07–1.91). Cumulative meta-analysis showed a trend of association as information accumulates. The results were affected by population origin and study quality criteria. The meta-analyses for the risk of restenosis following stent angioplasty or after angioplasty and treatment with angiotensin-converting enzyme inhibitors produced non-significant results. The allele contrast random effects odds ratios with the 95% confidence intervals were 1.04(0.92–1.16) and 1.10(0.81–1.48), respectively. Regarding the effect of <it>ACE I/D </it>polymorphism on the response to treatment for the rest outcomes (coronary events, endothelial dysfunction, left ventricular remodeling, progression/regression of atherosclerosis), individual studies showed significance; however, results were discrepant and inconsistent.</p> <p>Conclusion</p> <p>In view of available evidence, genetic testing of <it>ACE I/D </it>polymorphism prior to clinical decision making is not currently justified. The relation between <it>ACE </it>genetic variation and response to treatment in CAD remains an unresolved issue. The results of long-term and properly designed prospective studies hold the promise for pharmacogenetically tailored therapy in CAD.</p

A comparison of renal function outcomes after nephron-sparing surgery and radical nephrectomy for nonsyndromic unilateral Wilms tumor.

Abstract OBJECTIVE: To better understand the impact of nephron-sparing surgery (NSS) on renal function in patients with nonsyndromic unilateral Wilms tumor (uWT), a group of such patients treated with NSS were compared with a stage-matched cohort managed with radical nephrectomy (RN). The recommended management of nonsyndromic uWT is RN. However, NSS may decrease the risk of long-term renal disease and associated comorbidities. MATERIALS AND METHODS: An international, multi-institutional review was conducted of nonsyndromic uWT cases managed with NSS and compared with a stage-matched RN cohort. Data were collected on demographics, oncologic characteristics and outcomes, serum creatinine, and estimated glomerular filtration rate (eGFR) calculated via Schwartz formula. RESULTS: Fifteen patients who underwent NSS (6 females and 9 males) met study criteria and were diagnosed at a median age of 2.5 years (range, 0.2-8.2 years) and followed for a median of 8.4 years (range, 0.5-31.8 years). The stage-matched RN cohort consisted of 15 patients (8 females and 7 males) diagnosed at a median age of 3.7 years (0.3-7.4) and followed for a median of 2.1 years (0.6-10.5 years). The median preoperative eGFR was 91.7 (39.4-237.7) and 149.9 (93.8-215.9) for NSS and RN, respectively, P=.026. The median eGFR at last follow-up was 135.3 (57.5-185.8) and 131.0 (98.6-161.2) for NSS and RN, respectively, P=.95. The median change in eGFR during the study period was a gain of 28.6 (-51.9 to 83.0) for the NSS cohort vs a loss of 19.1 (-54.7 to 25.2) for the RN cohort, P=.007. CONCLUSION: In a highly selected patient population with nonsyndromic uWT, NSS provides excellent renal function preservation when compared with RN. These data require validation via prospective investigation on a larger scale

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins