Applying biochemical and structural characterization of hydroxycinnamate catabolic enzymes from soil metagenome for lignin valorization strategies.

The biocatalytic production of fuels and chemicals from plant biomass represents an attractive alternative to fossil fuel-based refineries. In this context, the mining and characterization of novel biocatalysts can promote disruptive innovation opportunities in the field of lignocellulose conversion and valorization. In the present work, we conducted the biochemical and structural characterization of two novel hydroxycinnamic acid catabolic enzymes, isolated from a lignin-degrading microbial consortium, a feruloyl-CoA synthetase, and a feruloyl-CoA hydratase-lyase, named LM-FCS2 and LM-FCHL2, respectively. Besides establishing the homology model structures for novel FCS and FCHL members with unique characteristics, the enzymes presented interesting biochemical features: LM-FCS2 showed stability in alkaline pHs and was able to convert a wide array of p-hydroxycinnamic acids to their respective CoA-thioesters, including sinapic acid; LM-FCHL2 efficiently converted feruloyl-CoA and p-coumaroyl-CoA into vanillin and 4-hydroxybenzaldehyde, respectively, and could produce vanillin directly from ferulic acid. The coupled reaction of LM-FCS2 and LM-FCHL2 produced vanillin, not only from commercial ferulic acid but also from a crude lignocellulosic hydrolysate. Collectively, this work illuminates the structure and function of two critical enzymes involved in converting ferulic acid into high-value molecules, thus providing valuable concepts applied to the development of plant biomass biorefineries. KEY POINTS: • Comprehensive characterization of feruloyl-CoA synthetase from metagenomic origin. • Novel low-resolution structures of hydroxycinnamate catabolic enzymes. • Production of vanillin via enzymatic reaction using lignocellulosic hydrolysates.

Comparative assessment of LDL-C and VLDL-C estimation in familial combined hyperlipidemia using Sampson's, Martin's and Friedewald's equations.

BACKGROUND: Sampson et al. developed a novel method to estimate very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) in the setting of hypertriglyceridemia. Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia in which lipoprotein composition interferes with LDL-C estimation. This study aimed to evaluate performance of LDL-C using this new method (LDL-S) compared with LDL-C estimated by Friedewald's and Martin eq. (LDL-F, LDL-M) in FCHL. METHODS: Data were collected from 340 subjects with confirmed FCHL. Concordance for VLDL-C measured by ultracentrifugation and LDL-C estimated using these measures compared to Sampson's, Martin's and Friedewald's equations was performed using correlation coefficients, root mean squared error (RMSE) and bias. Also, concordance of misclassified metrics according to LDL-C (< 70 and < 100 mg/dL) and Apo B (< 80 and < 65 mg/dL) thresholds were assessed. RESULTS: Sampson's equation was more accurate (RMSE 11.21 mg/dL; R2 = 0.88) compared to Martin's (RMSE 13.15 mg/dL; R2 = 0.875) and the Friedewald's equation (RMSE 13.7 mg/dL; R2 = 0.869). When assessing performance according to LDL-C, Sampson's had highest correlation and lowest RMSE compared to other equations (RMSE 19.99 mg/dL; R2 = 0.840). Comparing performance strength across triglyceride levels, Sampson's showed consistently improved correlations compared to Martin's and Friedewald's formulas for increasing triglycerides and for the FCHL phenotype of mixed dyslipidemia. Sampson's also had improved concordance with treatment goals. CONCLUSIONS: In FCHL, VLDL-C and LDL-C estimation using Sampson's formula showed higher concordance with lipid targets assessed using VLDL-C obtained by ultracentrifugation compared with Friedewald's and Martin's equations. Implementation of Sampson's formula could improve treatment monitoring in FCHL.

FAMILIAL COMBINED HYPERLIPIDEMIA: CURRENT KNOWLEDGE, PERSPECTIVES, AND CONTROVERSIES.

Familial combined hyperlipidemia (FCHL) is the most prevalent primary dyslipidemia; however, it frequently remains undiagnosed and its precise definition is a subject of controversy. FCHL is characterized by fluctuations in serum lipid concentrations and may present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B. FCHL is an oligogenic primary lipid disorder, which can occur due to the interaction of several contributing variants and mutations along with environmental triggers. Controversies surrounding the relevance of identifying FCHL as a cause of isolated hypertriglyceridemia and a differential diagnosis of familial hypertriglyceridemia are offset by the description of associations with USF1 and other genetic traits that are unique for FCHL and that are shared with other conditions with similar pathophysiological mechanisms. Patients with FCHL are at an increased risk of cardiovascular disease and mortality and have a high frequency of comorbidity with other metabolic conditions such as type 2 diabetes, non-alcoholic fatty liver disease, steatohepatitis, and the metabolic syndrome. Management usually requires lipid-lowering therapy directed toward reducing cholesterol and triglyceride concentrations along with cardiovascular risk protection. In recent years, the number of research studies on FCHL has been decreasing, mainly due to a lack of recognition of its impact on disease burden and comorbidity and the complexity in identifying probands for studies. This creates areas of opportunity to develop research for FCHL in epidemiology, genetics, pathophysiology, therapeutics, and cardiovascular risk management, which are discussed in depth in this review. (REV INVEST CLIN. 2018;70:224-36).

Performance of LDL-C calculated with Martin's formula compared to the Friedewald equation in familial combined hyperlipidemia.

BACKGROUND AND AIMS: A novel method to estimate low density lipoprotein cholesterol (LDL-C) has been proposed by Martin et al. This may permit a more accurate estimation of cardiovascular risk, however, external validation is needed. Here, the performance of LDL-C using this new method (LDL-N) is compared with LDL-C estimated with Friedewald equation (LDL-F) in familial combined hyperlipidemia (FCHL), a common primary dyslipidemia in which apolipoprotein B containing particle composition is abnormal and interferes with LDL-C estimation. METHODS: A total of 410 FCHL subjects were included. LDL-C was estimated with both the Friedewald equation (LDL-F) and the novel formula (LDL-N). Apolipoprotein B levels and non- HDL-C were recorded. The correlation and concordance between LDL-F and LDL-N and both Apolipoprotein B and non-HDL-C levels were calculated. Analysis stratifying for triglyceride tertiles and FCHL lipid phenotypes was also carried out. RESULTS: The correlations between LDL-N and Apo B and non-HDL-C were ρ = 0.777 (95%CI 0.718-0.825) and ρ = 0.735 (95%CI 0.648-0.816), respectively. The corresponding correlations for LDL-F were ρ = 0.551(95%CI 0.454-0.637) and ρ = 0.394 (95%CI 0.253-0.537), respectively. In mixed dyslipidemia or isolated hypertriglyceridemia, these correlations were significantly better using LDL-N. With respect to concordance, LDL-N performed significantly better than LDL-F when considering apoB <90 mg/dL (κLDL-N = 0.495 vs. κLDL-F = 0.165) and non-HDL-C <130 (κLDL-N = 0.724 vs. κLDL-F = 0.253). CONCLUSIONS: In FCHL, LDL-C estimation using Martin's formula showed greater correlation and concordance with non-HDL-C and Apo B compared with the Friedewald equation.

Determinants of VLDL composition and apo B-containing particles in familial combined hyperlipidemia.

BACKGROUND: In familial combined hyperlipidemia (FCHL) the severity of the dyslipidemia is determined by an overproduction of VLDL (very low density lipoprotein) particles and by its abnormal lipid composition. However, few are known regarding the metabolic factors that determine these abnormalities. We investigated the impact of metabolic factors on the number of atherogenic particles (apolipoprotein B level (apoB)) and the triglyceride content of very low-density lipoproteins (VLDLs-TG). METHODS: A cross-sectional study done in FCHL subjects and gender and age-matched healthy subjects. A clinical assessment, lipid profile and plasma concentrations of insulin, apolipoprotein CIII (apo CIII), apolipoprotein AII (apo AII), high sensitive C-reactive protein (HS-CRP), adiponectin and leptin were documented in 147 FCHL patients and 147 age-matched healthy subjects. Multivariate regression models were performed to investigate the independent determinants of VLDL-TG and apo B levels adjusting for confounding factors. RESULTS: The variables that determined the VLDL-triglyceride content as a surrogate of VLDL composition were apo CIII (ß=0.365, p<0.001), insulin (ß=0.281, p<0.001), Apo AII (ß=0.145, p<0.035), and adiponectin levels (ß=-0.255, p<0.001). This model explained 34% of VLDL composition (VLDL-TG) variability. However, none of these variables were independent contributors of apo B-containing particles. CONCLUSIONS: In patients with FCHL apo CIII, apo AII and adiponectin are major novel factors determining the VLDL particle composition. However, such factors do not explain apo B-containing particles.

Factors associated with postprandial lipemia and apolipoprotein A-V levels in individuals with familial combined hyperlipidemia.

BACKGROUND: Alterations in postprandial metabolism have been described in familial combined hyperlipidemia (FCH); however, their underlying mechanisms are not well characterized. We aimed to identify factors related to the magnitude of postprandial lipemia and apolipoprotein (apo) A-V levels in subjects with FCH. METHODS: FCH cases (n = 99) were studied using a standardized meal test. Abdominal obesity was assessed using the waist to hip ratio (WHR). A linear regression model was performed to investigate the variables associated with the triglycerides incremental area under the curve (iAUC). Independent associations between metabolic variables and apo A-V iAUC were also investigated in a randomly selected subgroup (n = 44). The study sample was classified according to the presence of fasting hypertriglyceridemia (≥150 mg/dL) and abdominal obesity (WHR ≥0.92 in men and ≥0.85 in women) to explore differences in parameters. RESULTS: The fasting apo B-48 levels (r = 0.404), and the WHR (r = 0.359) were independent factors contributing to the triglycerides iAUC (r2 = 0.29, P < 0.001). The triglycerides iAUC was independently associated with the apo A-V iAUC (r2 = 0.54, P < 0.01). Patients with both hypertriglyceridemia and abdominal obesity showed the most robust triglycerides and apo A-V postprandial responses. CONCLUSIONS: In patients with FCH the fasting apo B-48 level is the main factor associated with postprandial lipemia. Abdominal obesity also contributes to the magnitude of the postprandial response.The triglycerides postprandial increment is the principal factor associated with the apo A-V postprandial response.

Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia.

Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explain the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia.

S323I polymorphism of the C5L2 gene was not identified in a Chinese population with familial combined hyperlipidemia or with type 2 diabetes.

C5L2, a G protein-coupled receptor, is known to be a functional receptor of acylation-stimulating protein, which is a stimulator of triglyceride synthesis and glucose transport. A novel C5L2 variant (S323I) was identified and its association with familial combined hyperlipidemia (FCH) was recently reported. We looked for this SNP in three Chinese ethnic groups, including Han, Uygur, and Kazakh controls and patients with FCH and type 2 diabetes. One hundred and eighty-two unrelated subjects (77 of Han, 57 of Uygur, and 48 of Kazakh) with FCH were genotyped by direct sequencing, and 852 subjects (342 of Han, 338 of Uygur, 172 of Kazakh) with type 2 diabetes and 200 healthy controls (67 of Han, 72 of Uygur, and 61 of Kazakh) chosen from a cardiovascular risk survey study were genotyped with PCR-RFLP analysis. All 182 subjects with FCH, 99.5% of the type 2 diabetes patients and 100% of the healthy controls were successfully genotyped. Neither the FCH subjects nor the type 2 diabetes patients were found to have the S323I variant. This variant was also not identified in the healthy controls. We found no evidence to demonstrate that the S323I polymorphism contributes to familial combined hyperlipidemia or type 2 diabetes in the Chinese population.

Xantomas eruptivos: manifestación cutánea de desórdenes de las lipoproteínas / Eruptive xanthomas: skin manifestation of the lipoprotein disorders

Los xantomas constituyen tumores cutáneos, y se presentan por depósitos de lipoproteínas en los macrófagos tisulares. Clínicamente se manifiestan como lesiones papulosas o nodulares de color amarillento, estando relacionada su distribución con las diferentes formas clínicas de presentación. Aunque no se observan con frecuencia, su presencia puede alertar sobre la existencia de alteraciones en los niveles lipídicos en sangre, y es por lo que se presentó este caso, donde la presencia de los xantomas fue indicador de un incremento de los niveles de colesterol y triglicéridos, lo que pudo constituir un importante factor de riesgo para que la paciente presentara alteraciones en otros sistemas...

Xanthomas are skin tumors, and they present as a cause of lipoprotein deposits in tissue macrophages. Clinically they take the form of yellow papular or nodular lesions, being related its distribution with their different forms of presentation. Though they are not very frequent, their presence can alert about the existence of alterations in the lipid levels in blood. That is why we presented this case, where the presence of xanthomas was an indicator of the cholesterol and triglycerides level increase, what probably was an important risk fact for the patient to present alterations in other systems...

[Fifty years studying hiperlipidemias: the case of familial combined hyperlipidemia]. / Cincuenta años de estudio de las hiperlipidemias primarias: El caso de la Hiperlipidemia familiar combinada.

Familial combined hyperlipidemia (FCHL) is the most frequent primary dyslipidemia. Its manifestations include hypercholesterolemia, hypertriglyceridemia or the combination of both abnormalities. In spite of its high frequency, the proper diagnosis is rarely done. For this purpose, the measurement of a lipid profile is required in at least three first-degree relatives. A critical review of the current literature in this field is presented in this paper. Prospective studies have confirmed the atherogenicity of the disease. It is possible to identify the FCHL causal genes with the current methodology because it is an oligogenic disease. Based on the use of new technologies, several loci that regulate apolipoprotein B concentrations have been identified. In addition it was demostrated that variations of the activity or the expression of various nuclear factors (USF1, TCF7L2, HNF4alfa) have a major role in the pathophysiology of FCHL. These nuclear factors regulate the expression of multiple genes involved in the metabolism of lipids or carbohydrates.

Cincuenta años de estudio de las hiperlipidemias primarias: el caso de la hiperlipidemia familiar combinada / Fifty years studying hiperlipidemias: the case of familial combined hyperlipidemia

La hiperlipidemia familiar combinada (HLFC) es la dislipidemia primarias más frecuente en México. Se manifiesta por hipercolesterolemia, hipertrigliceridemia o la combinación de estos defectos. Pese a su frecuencia, pocas veces es diagnosticada con certidumbre. Se requiere del estudio de al menos tres familiares directos para corroborar el diagnóstico. En esta revisión se describen los avances ocurridos en los últimos años sobre la fisiopatología y diagnóstico de la hiperlipidemia familiar combinada. Estudios prospectivos han confirmado la aterogenicidad de la enfermedad. Por ser una enfermedad oligogénica es factible identificar los genes involucrados con los recursos ahora existentes. Gracias al uso de nuevas tecnologías, se han identificado regiones cromosómicas que determinan la concentración de la apolipoproteína B y se demostró que diferencias en la actividad o concentración de varios factores nucleares (USF1, TCF7L2, HNF4alfa) juegan un papel importante en la fisiopatología de la HLFC. Los factores nucleares antes mencionados regulan la expresión de múltiples genes que participan en el metabolismo de lípidos y carbohidratos.

Familial combined hyperlipidemia (FCHL) is the most frequent primary dyslipidemia. Its manifestations include hypercholesterolemia, hypertriglyceridemia or the combination of both abnormalities. In spite of its high frequency, the proper diagnosis is rarely done. For this purpose, the measurement of a lipid profile is required in at least three first-degree relatives. A critical review of the current literature in this field is presented in this paper. Prospective studies have confirmed the atherogenicity of the disease. It is possible to identify the FCHL causal genes with the current methodology because it is an oligogenic disease. Based on the use of new technologies, several loci that regulate apolipoprotein B concentrations have been identified. In addition it was demostrated that variations of the activity or the expression of various nuclear factors (USF1, TCF7L2, HNF4alfa) have a major role in the pathophysiology of FCHL. These nuclear factors regulate the expression of multiple genes involved in the metabolism of lipids or carbohydrates.

Identification of two common variants contributing to serum apolipoprotein B levels in Mexicans.

BACKGROUND AND PURPOSE: Although the Mexican population has a high predisposition to dyslipidemias and premature coronary artery disease, this population is underinvestigated for the genetic factors conferring the high susceptibility. This study attempted to determine these genetic factors. METHODS AND RESULTS: First, we investigated apolipoprotein B (apoB) levels in Mexican extended families with familial combined hyperlipidemia using a two-step testing strategy. In the screening step, we screened 5721 single-nucleotide polymorphisms (SNPs) for linkage signals with apoB. In the test step, we analyzed the 130 SNPs residing in regions of suggestive linkage signals for association with apoB. We identified significant associations with two SNPs (ie, rs1424032 [P=6.07x10(-6)] and rs1349411 [P=2.72x10(-4)]) that surpassed the significance level for the number of tests performed in the test step (P<3.84x10(-4)). Second, these SNPs were tested for replication in Mexican hyperlipidemic case-control samples. The same risk alleles as in the families with familial combined hyperlipidemia were significantly associated (P<0.05) with apoB in the case-control samples. The rs1349411 resides near the apoB messenger RNA editing enzyme (APOBEC1) involved in the processing of APOB messenger RNA in the small intestine. The rs1424032 resides in a highly conserved noncoding region predicted to function as a regulatory element. CONCLUSIONS: We identified two novel variants, rs1349411 and rs1424032, for serum apoB levels in Mexicans.

Ezetimibe treatment of pediatric patients with hypercholesterolemia.

OBJECTIVE: To review the efficacy of ezetimibe monotherapy for treatment of hypercholesterolemia in pediatric patients. STUDY DESIGN: This is a retrospective review of all pediatric patients who received ezetimibe monotherapy as treatment for hypercholesterolemia and for whom follow-up clinical and lipid results were available. Of 36 identified patients, 26 had lipoprotein profiles suggestive of familial hypercholesterolemia (FH), and 10 had profiles suggestive of familial combined hyperlipidemia (FCHL). RESULTS: After a mean 105 days of treatment with ezetimibe (range, 32-175 days), total cholesterol (TC) levels decreased from 7.3 +/- 1.0 mmol/L to 5.7 +/- 1.0 mmol/L (P < .0001), and low-density lipoprotein cholesterol (LDL-C) levels decreased from 5.3 +/- 0.9 mmol/L to 3.9 +/- 0.8 (P < .0001) in patients with FH. In patients with FCHL, TC levels decreased from 6.4 +/- 2.0 mmol/L to 5.6 +/- 0.4 mmol/L (P < or = .002), and LDL-C levels decreased from 4.7 +/- 1.0 mmol/L to 3.8 +/- 0.6 mmol/L (P < or = .005). For all patients, the mean decrease in individual LDL-C values was 1.5 +/- 0.9 mmol/L or 28%. There was no significant change in triglyceride or high-density lipoprotein cholesterol levels with ezetimibe. Patients were maintained on ezetimibe with no adverse effects attributable to the medication for as long as 3.5 years. At a mean of 13.6 months (range, 1-44 months) after the initiation of ezetimibe, LDL-C levels remained decreased at 4.0 +/- 0.6 mmol/L. CONCLUSIONS: In this small retrospective series of children and adolescents with hypercholesterolemia, ezetimibe was safe and effective in lowering LDL-C levels.

Familial combined hyperlipidemia in Mexicans: association with upstream transcription factor 1 and linkage on chromosome 16q24.1.

OBJECTIVE: To investigate the largely unknown genetic component of the common lipid disorder, familial combined hyperlipidemia (FCHL) in Mexicans, we analyzed the upstream transcription factor 1 (USF1) gene that was recently associated with FCHL and high triglycerides (TG) in Finns. We also analyzed the Mexican FCHL families for 26 microsatellite markers residing in the seven chromosomal regions on 2p25.1, 9p23, 10q11.23, 11q13, 16q24.1, 19q13, and 21q21, previously linked to FCHL in whites. METHODS AND RESULTS: We genotyped 314 individuals in 24 Mexican families for 13 SNPs spanning an 88-kb region, including USF1. The FCHL and TG traits showed significant evidence for association with 3 SNPs, hCV1459766, rs3737787, and rs2073658, and haplotype analyses further supported these findings (probability values of 0.05 to 0.0009 for SNPs and their haplotypes). Of these SNPs, hCV1459766 is located in the F11 receptor (F11R) gene, located next to USF1, making it difficult to exclude. Importantly, the association was restricted to a considerably smaller region than in the Finns (14 kb versus 46 kb), possibly because of a different underlying linkage disequilibrium structure. In addition, 1 of the 7 regions, 16q24.1, showed suggestive evidence for linkage (a lod score of 2.6) for total cholesterol in Mexicans. CONCLUSIONS: This study, the first to extensively investigate the genetic component of the common FCHL disorder in Mexicans, provides independent evidence for the role of USF1 in FCHL in an outbred population and links the 16q24.1 region to an FCHL-component trait in Mexicans.

Familial combined hyperlipidemia: controversial aspects of its diagnosis and pathogenesis.

Familial combined hyperlipidemia is the most frequent cause of primary dyslipidemia in Mexico. Its manifestations include hypercholesterolemia, hypertriglyceridemia, or a combination of both. Despite its high frequency, a proper diagnosis is rarely made. Assessment of the lipid profiles of at least three first-degree relatives is necessary. The diagnosis of familial combined hyperlipidemia in a family not only leads to the identification of other affected family members but, more important, allows cardiovascular risk stratification of those affected. Prospective studies have confirmed the atherogenicity of the disease. A critical review of the current literature in this field is presented in this article. Although three screenings of the genome have been completed, the genes responsible for this disorder have not been identified. Limitations with respect to the characterization of affected subjects and the heterogeneity of the disease are among possible explanations. However, familial combined hyperlipidemia, because of its high prevalence, must be given greater priority. It represents a great challenge for physicians involved in the treatment of dyslipidemic patients.

Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families.

Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 in Finnish, Chinese, German and US families. We studied seven extended Mexican families with 153 members, including 64 affected subjects. A total of 11 markers were genotyped, including D1S104 which has been linked to FCHL in other studies. Two point linkage analysis for the FCHL phenotype, and for the elevated triglyceride (TG) trait, allowing for heterogeneity, gave a maximum HLOD of 1.67 (alpha = 0.49) and 1.93 (alpha = 0.43) at D1S2768 (2.69 cM proximal to D1S104) respectively. Heterogeneity and non-parametric (NPL) multipoint analyses for the FCHL phenotype and the TG trait showed maximum HLODs of 1.27 (alpha = 0.46) and 1.64 (alpha = 0.38), and NPLs of 4.00 (P = 0.0001) and 3.68 (P = 0.0003) near D1S2768, respectively. In addition, analysis of four candidate genes putatively involved in the expression of FCHL showed no evidence of linkage for the LCAT gene or the APOA1/C3/A4/A5 gene cluster. However, we cannot exclude the participation of these genes, or the LIPC and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG or elevated total cholesterol (TC) traits in our families. In conclusion, our data confirm the involvement of a major susceptibility locus on chromosome 1q21-q23 in FCHL Mexican families, consistent with findings in other populations.

Genetic factors play an important role in the pathogenesis of hyperlipidemia post-transplantation.

BACKGROUND: Our purpose was to identify factors associated with hyperlipidemia post-transplantation in a Hispanic population. METHODS: From 1985 to 1999, a kidney graft survival longer than 3 months occurred in 293 cases at the Instituto Nacional de la Nutrición. Most of the patients living in Mexico City were included (n = 83). The evaluation included a questionnaire, blood samples, and assessment of body composition and dietary habits. As many as possible first-degree relatives were studied. RESULTS: Women had higher values of cholesterol (236 +/- 51 versus 215 +/-41; P < 0.05), low-density lipoprotein cholesterol (147 +/- 42 versus 131 +/- 34; P = 0.05), high-density lipoprotein cholesterol (57.3 +/- 14 versus 47.9 +/- 14; P = 0.002) and high-density lipoprotein-2 cholesterol. Isolated hypercholesterolemia was the most common lipid abnormality (40.9%), followed by mixed hyperlipidemia. Lipoprotein (a) greater than 30 mg/dL was found in 13 cases. Familial combined hyperlipidemia (FCHL) in the patient's relatives was a marker for dyslipidemia (odds ratio, 7.04; 95% confidence interval, 1.2 to 59.7). These cases had a worse lipid profile. Cyclosporine-treated FCHL patients had higher lipid levels compared with the non-FCHL, cyclosporine-treated patients. The effects of cyclosporine on the lipid levels were lower, but significant, after the exclusion of the FCHL cases. CONCLUSION: Post-transplant dyslipidemia is determined by genetic and environmental factors. FCHL in the patient's relatives was associated with post-transplant hyperlipidemia; an additive effect with cyclosporine was found. The evaluation of the lipid profile of relatives may be useful for the assessment of the risk of post-transplant dyslipidemia.

Lack of agreement between the plasma lipid-based criteria and apoprotein B for the diagnosis of familial combined hyperlipidemia in members of familial combined hyperlipidemia kindreds.

Our objective was to analyze the concordance between abnormally high-cholesterol and triglyceride concentrations and increased apoliprotein B (apoB) concentrations for considering subjects as affected in familial combined hyperlipidemia (FCHL) kindreds. Twenty-two FCHL families (n = 217) were included. There was a lack of agreement in the identification of the abnormal subjects when several cholesterol- and triglyceride-based criteria were compared against various apoprotein B-based criteria. The agreement, measured as kappa coefficients, between 14 lipid-based criteria and 8 apoB concentrations is reported. For the most frequently used criterion (> or = 90th percentile for cholesterol or triglyceride concentrations), the agreement was low for all apoB levels (kappa, 0.42 to 0.49). A concentration of triglycerides > or = 150 mg/dL and cholesterol > or = 200 mg/dL was the only criterion with a kappa value above 0.6; the acceptable agreement was found with an apoB concentration > or = 120 mg/dL (kappa = 0.604). In conclusion, the data reported here clearly show that a large degree of diagnostic uncertainty exists in the categorization as normal or abnormal of members of FCHL kindred. Different diagnostic criteria would result in conflicting results. This is a critical issue, depending on the diagnostic criteria used, completely different conclusions could result from the linkage analysis in the FCHL studies.

Dislipidemia en el escolar y adolescente / Dislipidemia in school children and adolescents

Las enfermedades cardiovasculares constituyen la primera causa de morbimortalidad en la población adulta de la mayoría de los países desarrollados y también en Chile. Entre éstas, la primera causa individual corresponde a la enfermedad coronaria, cuya relación con la concentración de lípidos plasmáticos, especialmente colesterol de lipoproteína de baja densidad (LDL), ha sido claramente establecida

Xantomas eruptivos / Eruptives xanthomas

Se presentan dos pacientes con xantomas eruptivos. Se describe la clínica e histopatología de esta enfermedad y se enumeran los diagnósticos diferenciales. Se destaca la importancia de dicha patología en el descubrimiento de una hiperlipidemia muchas veces ignorada, que puede poner en peligro la vida del paciente