Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

<p>Abstract</p> <p>Background</p> <p>Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including <it>LPL</it>, <it>APOA5 </it>and <it>APOE</it>. The combined analysis of these polymorphisms could produce clinically meaningful complementary information.</p> <p>Methods</p> <p>A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the <it>LPL</it>-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the <it>APOA5</it>-S19W (rs3135506) and -1131T/C (rs662799) variants, and the <it>APOE </it>polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption.</p> <p>Results</p> <p>We found a significant lowering effect of the <it>LPL</it>-HindIII and S447X polymorphisms (<it>p </it>< 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the <it>APOE</it>-ε4 allele were significantly associated with an independent additive TG-raising effect (<it>p </it>< 0.05, <it>p </it>< 0.01, <it>p </it>< 0.001, <it>p </it>< 0.0001 and <it>p </it>< 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (<it>p </it>< 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; <it>p </it>= 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; <it>p </it>< 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; <it>p </it>< 0.001) were associated with HTG.</p> <p>Conclusion</p> <p>Our results showed a significant independent additive effect on TG levels of the <it>LPL </it>polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of <it>APOA5</it>, and the ε4 allele of <it>APOE </it>in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.</p

2006 GEP-ISFG collaborative exercise on mtDNA: reflections about interpretation, artefacts, and DNA mixtures

We report the results of the seventh edition of the GEP-ISFG mitochondrial DNA (mtDNA) collaborative exercise. The samples submitted to the participant laboratories were blood stains from a maternity case and Simulated forensic samples, including a case of mixture. The success rate for the blood stains was moderate (similar to 77%); even though four inexperienced laboratories concentrated about one-third of the total errors. A similar success was obtained for the analysis of mixed samples (78.8% for a hair-saliva mixture and 69.2% for a saliva-saliva Mixture). Two laboratories also dissected the haplotypes contributing to the saliva-saliva mixture. Most of the errors were due to reading problems and misinterpretation of electropherograms, demonstrating once more that the lack of a solid devised experimental approach is the main cause of error in mtDNA testing. (C) 2007 Elsevier B.V. All rights reserved