ABSTRACT
Introducción. La prevalencia del sobrepeso, la obesidad y algunas enfermedades crónicas no transmisibles ha aumentado; sus causas pueden ser genéticas, epigenéticas o ambientales, por lo cual es importante evaluar la variabilidad en estas interacciones. Objetivo. Analizar las relaciones entre nueve polimorfismos de nucleótido simple de los genes LEP (rs2167270), LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) y APOA4 (rs5095, rs675, rs5110), y los fenotipos asociados al sobrepeso, la obesidad y otras enfermedades concomitantes. Materiales y métodos. Se evaluaron parámetros clínicos y antropométricos en 144 sujetos del estado Sucre, Venezuela, 76 hombres y 68 mujeres , con medias de edad de 29,93±8,29 y 32,49±11,15 años, respectivamente. Se hizo la genotipificación de los polimorfismos seleccionados mediante enzimas de restricción; se estudiaron las asociaciones entre genotipo y riesgo, y se compararon los promedios de las medidas antropométricas y bioquímicas previamente ajustadas a variables biológicas y ambientales. Resultados. Según el índice de masa corporal (IMC), el 38,9 % de los individuos tenía sobrepeso (25=IMC=29,9 kg/m 2 ) y el 20,1 %, obesidad (IMC=30 kg/m 2 ) . Las frecuencias genotípicas y alélicas de los grupos con un índice de masa corporal normal y uno alto (sobrepeso y obesidad) resultaron similares. Solo se encontró asociación entre el genotipo ancestral A/A del rs5742911 y el riesgo alto por los niveles de la lipoproteína de alta densidad o colesterol HDL (OR=2,944, IC 95% 1,446-5,996; p=0,003). La diferencia entre los promedios corregidos de colesterol HDL para los genotipos del rs5742911 resultó significativa (p=0,005) (A/A: 41,50±14,81 mg/dl; A/G: 45,00±12,07 mg/dl; G/G: 47,17±9,43 mg/dl). Conclusión. En la mayoría de las variantes genéticas estudiadas, se registró la asociación con el sobrepeso y la obesidad de los genotipos ancestrales, aunque sin ser significativa. El polimorfismo rs5742911 podría resultar útil como indicador del riesgo de enfermedades crónicas.
Introduction: Overweight, obesity and some chronic diseases have become more prevalent recently. It is well known that their causes may be genetic, epigenetic, environmental, or a mixture of these. Objective: To analyze the relationship between nine single nucleotide polymorphisms of genes LEP (rs2167270) , LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) and APOA4 (rs5095, rs675, rs5110) with obesity-related phenotypes and other comorbidities. Material and methods: We recruited 144 adults (76 males and 68 females, with average ages of 29.93±8.29 and 32.49±11.15 years, respectively) in the State of Sucre, Venezuela. Clinical and anthropometric parameters were obtained. Genotype-risk associations were studied. We then compared the averages registered for anthropometric and biochemical variables previously adjusted for biological and environmental factors. Results: According to the body mass index, 38.9% of the individuals in the sample were overweight (25=BMI=29.9 kg/m 2 ) and 20.1% were obese (BMI=30 kg/m 2 ). Genotype and allele frequencies did not differ statistically for groups with normal and high body mass index (overweight plus obesity). The association between LDLR rs5742911 ancestral genotype A/A and high risk condition related to HDL-cholesterol was the only one found to be significant (OR=2.944, 95% CI: 1.446-5.996; p=0.003). The difference in adjusted mean HDL-cholesterol for LDLR rs5742911 genotypes was statistically significant (p=0.005) (A/A: 41.50±14.81 mg/dL; A/G: 45.00±12.07 mg/dL; G/G: 47.17±9.43 mg/dL). Conclusions: For most of the genetic variants studied, there was an association with the presence of overweight and obesity among ancestral genotype carriers, although this was not statistically significant. The rs5742911 polymorphism may be useful as an indicator of a risk of chronic diseases.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Apolipoproteins A/genetics , Receptors, LDL/genetics , Leptin/genetics , Polymorphism, Single Nucleotide , Overweight/genetics , Socioeconomic Factors , Venezuela/epidemiology , Blood Glucose/analysis , Anthropometry , Chronic Disease/epidemiology , Dyslipidemias/genetics , Dyslipidemias/epidemiology , Overweight/epidemiology , Genetic Association Studies , Habits , Life Style , Lipids/blood , Obesity/genetics , Obesity/epidemiologyABSTRACT
The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.
A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.
Subject(s)
Humans , Lipoprotein(a)/physiology , Apolipoproteins A/chemistry , Apolipoproteins A/genetics , Lipoprotein(a)/analysis , Lipoprotein(a)/metabolism , Risk FactorsABSTRACT
Metabolic syndrome [MetS] is one of the most important risk factors for cardiovascular diseases. The aim of this study was to determine the association between the G360T polymorphism of apolipoprotein A-IV gene and MetS. For this cross sectional study, 782 individuals, aged >19 years, were selected randomly from among TLGS participants; these included 325 men [61 with MetS and 264 controls], and 457 women [131 with MetS and 326 controls]. Anthropometric and biochemical parameters were measured. The Apo A-IV gene polymorphism was studied using the PCR-RFLP method by Fnh4HI restriction enzyme. Frequencies of the G and T alleles in men with MetS and those without were 85.2, 14.8, and 83.3, 16.7%, respectively, and in women with and without MetS these were 82.4, 17.6, and 85.9, 14.1%, respectively, values not significant. The GG and TT genotypes had the highest and lowest frequency, respectively [84.4% and 0.3%]. Analyses of data showed that presence of T allele was significantly associated with lower levels of HDL-C [p<0.05] in women with MetS, and with lower apolipoprotein CIII levels [p <0.05] in normal women, and higher diastolic blood pressure [p <0.05] in men without MetS. The findings of the current study showed significant effects on HDL-C levels in women with MetS. Considering the association observed between the G360T polymorphism of Apo A-IV gene and lipid factors in women with MetS and the high prevalence of this syndrome in Iranian women, further studies recommended to assess the association of Apo AIV gene variation with lipids factors for prevention and treatment of the syndrome
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Apolipoproteins A/genetics , Polymorphism, Genetic , Cross-Sectional Studies , GenotypeABSTRACT
Triglyceride concentrations are an independent risk factor for coronary heart disease. Apolipoprotein A5 gene (APOA5) has an important role determining triglyceride metabolism and it is a potential cardiovascular risk. However the mechanisms for these actions are not well-known. Despite the different allelic frequency of its major polymorphisms in different populations, multiple studies have shown consistent associations between these variants and fasting triglycerides. Variations in the APOA5 gene have also been associated with postprandial triglycerides, as well as with different sizes of lipoproteins and other markers. Moreover, some of the APOA5 gene variants have been associated with ischemic heart disease, stroke, and carotid intima media thickness, although the references on this issue are scanty and contradictory. This may be due to the presence of gene-environment interactions that have been poorly studied until now. Among the few studies that have examined the infuence of environmental factors on possible genetic variations, the most important are those that contemplate possible gene-diet interactions. However, the evidence is still scarce and more research is required in the feld of nutrigenomics. To understand the impact of this gene on cardiovascular disease, we review the genetic functionality and variability of APOA5, its associations with intermediate and fnal phenotypes and gene-environment interactions detected.
Subject(s)
Humans , Apolipoproteins A/genetics , Cardiovascular Diseases/genetics , Polymorphism, Genetic/genetics , Apolipoproteins A/physiology , Hypertriglyceridemia/genetics , Phenotype , Risk FactorsABSTRACT
Introducción: Diversas variantes genéticas han sido relacionadas al desarrollo de enfermedad coronaria y/o sus factores de riesgo; entre ellas, los polimorfismos S19W y -1131T>C del gen que codifica para la apolipoproteína A5 (APOA5). Así, el objetivo del presente estudio fue investigar la posible asociación entre las variantes S19W y -1131T>C del gen APOA5 y enfermedad coronaria en individuos chilenos. Métodos: Se evaluaron 425 sujetos adultos, no relacionados; 209 pacientes con enfermedad coronaria (EC) comprobada por angiografía (estenosis→ 70 por ciento), con edades entre 33 y 74 años, y 216 individuos controles (30 a 68 años). La genotipificación de los polimorfismos S19Wy -1131T>C del gen APOA5 fue realizada mediante la técnica de PCR-RFLP Resultados: La distribución de los genotipos para el polimorfismo S19W del gen APOA5 en el grupo casos (SS: 80 por ciento, SW: 19 por ciento y WW: 1 por ciento) y en el grupo control (SS: 82 por ciento, SW: 17 por ciento y WW: 1 por ciento) fue semejante (p=NS). La distribución genotípica para el polimorfismo -1131T>C en pacientes con EC (TT: 56 por ciento, TC: 37 por ciento, y CC: 7 por ciento) y controles (TT: 63 por ciento, TC: 30 por ciento y CC: 7 por ciento) fue similar (p=NS). Las ORs relacionadas a los alelos mutados 19W (1.12; I.C.95 por ciento, 0.72- 1.74, p=NS)y-1131C (1.19; I.C.95 por ciento,, 0.87- 1.63, p=NS), confirman la ausencia de asociación. Por otro lado, las concentraciones de triglicéridos y glucosa en ayunas fueron significativamente más elevadas en los sujetos portadores de los alelos 19Wy -1131C, tanto en casos como en controles (p<0.05). Conclusión: La asociación observada entre las variantes genéticas de APOA5 y las altas concentraciones séricas de triglicéridos y glucosa, en ambos grupos, sugiere que estos polimorfismos podrían contribuir al desarrollo de la dislipidemia diabética; un reconocido factor de riesgo para enfermedad arterial coronaria.
Background: Several genetic variants have been linked to the development of coronary heart disease and/or their risk factors, including the S19Wand-1131T> C polymorphisms of the gene that encodes apolipoprotein A5 (APOA5). Thus, the objective of this study was to investigate the possible association between S19W and -1131T>C genetic variants ofAPOA5 and coronary disease in Chilean individuals. Methods: We evaluated 425 not related subjects; 209 patients with coronary artery disease (CAD) confirmed by angiography (stenosis→ 70 percent,), aged between 33 and 74 years, and 216 control individuals (30 to 68 years). The genotyping of S19W and -1131T>C polymorphisms of APOA5 gene was evaluated by PCR-RFLP. Results: The genotype distribution of S19W polymorphism of APOA5 gene in CAD patients (SS: 80 percent,, SW: 19 percent, WW: 1 percent>) and controls (SS: 82 percent,, SW: 17 percent, WW: 1 percent>) was similar (p = NS). In the same way the genotype distribution of-1131T>C genetic variant in CAD subjects (TT: 56 percent,, TC: 37 percent,, and CC: 7 percent>) and controls (TT: 63 percent,, TC: 30 percent, and CC: 7 percent) was equivalent (p = NS). The Odds ratios related to the mutant alleles 19W (1.12, 95 percent, Cl, 0.72 - 1.74, p = NS) and -1131C (1.19, 95 percent, Cl, 0.87 -1.63, p = NS) confirms the absence of association. On the other hand, the triglycerides and fasting glucose concentrations were significantly higher in subjects carrying the alleles 19W and -1131C, in both groups, CAD patients and controls (p <0.05). Conclusion: The observed association between genetic variants of APOA5 and higher serum levels of triglycerides and glucose, in both groups, suggesting that these polymorphisms could be contribute to the development of diabetic dyslipidemia, a known risk factor for coronary artery disease.
Subject(s)
Humans , Male , Adult , Female , Middle Aged , Apolipoproteins A/genetics , Coronary Disease/genetics , Blood Glucose , Polymorphism, Genetic , Triglycerides/blood , Coronary Disease/blood , Risk Factors , GenotypeABSTRACT
La hiperlipidemia por lipoproteína a -LDL más apo a- es un factor de riesgo vascular aterotrombótico, familiar, independiente y poderoso, llamativamente desconsiderado. Este trabajo tiene como objetivo su mejor diagnóstico y tratamiento.
Subject(s)
Humans , Apolipoproteins A/genetics , Cholesterol, HDL/metabolism , Cholesterol, LDL/genetics , Cholesterol, LDL/metabolism , Cardiovascular Diseases/pathology , Lipoprotein(a) , Lysine/pharmacology , Niacin/therapeutic use , Proline/pharmacologyABSTRACT
PURPOSE: Recent studies using human and mice reported that apolipoprotein A-V (APOA5) gene plays an important role in controlling triglyceride (TG) concentrations. The purpose of the present study was to investigate the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in the APOA5 gene and TG in subjects and to search for possible associations of the APOA5 gene variants and common haplotypes with hypertriglyceridemia (HTG). MATERIALS AND METHODS: We examined the case-control subjects including 100 HTG patients and 243 unrelated healthy control. The genes were screened for SNPs by direct sequencing in 48 genetically unrelated individuals. Six SNPs (-1390C>T, -1020G>A, -3A>G, V150M, G182C and 1259T>C) were genotyped in case and control populations. RESULTS: In this study, our results indicated a strong association between APOA5 SNP -3A>G and G182C and elevated TG levels (p<0.001). Analysis of the SNPs from APOA5 gene has identified major haplotype showing very strong association with HTG, CGGGTT (p<0.001). Likelihood ratio test (LRT) of these six SNPs revealed that haplotypes were strong independent predictors of HTG (p<0.001). Haplotype-trend logistic regression (HTR) analysis revealed a significant association between the CGGGGC (haplotype 2) and CGGGTT (haplotype 4) and HTG (OR=2.48, 95% CI=1.06-5.76 and OR=8.54, 95% CI=2.66-27.42, respectively). CONCLUSION: We confirm that the APOA5 variants are associated with triglyceride levels and the haplotype may be strong independent predictors of HTG among Koreans.
Subject(s)
Female , Humans , Male , Middle Aged , Apolipoproteins A/genetics , Case-Control Studies , Genetic Predisposition to Disease , Haplotypes , Hypertriglyceridemia/genetics , Korea , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Triglycerides/bloodABSTRACT
Genetic studies have suggested that polymorphisms of genes coding for apolipoproteins are significant determinants of serum lipoprotein and lipid levels in adults. However, only a few studies have investigated the association of these polymorphisms in children. Therefore, in the present investigation we studied the distribution of APOA1 -75 G>A, +83 C>T, APOC3 -482 C>T, -455 T>C and 3238 C>G, and APOA4 Q360H and T347S polymorphisms and their influence on plasma lipoprotein levels in children from a Brazilian northeastern admixed population. The seven polymorphic sites were genotyped in 414 children aged 5 to 15 years (mean 8.9 ± 2.9). The genotypes of the seven polymorphic sites were assessed by PCR-RFLP methods. The frequencies of the less common alleles were, in general, intermediate among parental populations, as expected. Strong linkage disequilibrium was detected between polymorphisms at the APOA1, APOC3 and APOA4 loci in this admixed population sample. Overall the genotype effects seen in adults were weaker or absent in children. The APOC3/-455 and APOA4 T347S variants showed significant effects on HDL cholesterol in girls (P = 0.033 and P = 0.016, respectively). Significantly higher plasma total (P = 0.003) and LDL cholesterol (P = 0.004) levels were observed in boys who were carriers of the 3238G allele at the APOC3/3238 C>G site. These results disclosed an overall absence of associations between these polymorphisms and lipids in children. This finding is not unexpected because expression of the effect of these polymorphisms might depend on the interaction with environmental variables both internal and external to the individual.
Subject(s)
Adolescent , Child , Child, Preschool , Humans , Apolipoprotein A-I/genetics , Apolipoproteins A/genetics , Apolipoproteins C/genetics , Lipids/blood , Polymorphism, Genetic/genetics , Apolipoprotein C-III , Brazil , Gene Frequency , Genetic Variation , Genotype , Lipids/genetics , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
En el presente trabajo se analizaron dos aspectos distintos del metabolismo lipoproteico. En el primero, en un estudio bioquímico clínico, se presentó un método rápido y simple de determinación de los polimorfismos de la apoE. La utilidad clínica de conocer el genotipo apoE fue evaluada correlacionando las isoformas de apoE con el espesor carotideo estimado con ecografía de ultrasonido. Los resultados mostraron que el genotipo apoE4 ejerce un efecto sobre la aterosclerosis carotídea, efecto que puede ser detectado antes que cualquier otro síntoma clínico. En la segunda parte de éste trabajo se ha analizado el metabolismo lipoproteico en ratones transgénicos expresando la apolipoproteína A-IV (apoA-IV) humana. Los resultados muestran que la apoA-IV tiene un rol pleiotrópico en el organismo, relacionado con la protección contra la aterosclerosis y con la regulación de la secreción gástrica
Subject(s)
Humans , Guinea Pigs , Middle Aged , Apolipoproteins A/genetics , Apolipoproteins E/genetics , Apolipoproteins , Lipoproteins/metabolism , Apolipoproteins E/physiology , Apolipoproteins E/blood , Apolipoproteins/physiology , Cholesterol, HDL , Cholesterol, LDL , Gene Expression , Lipoproteins/blood , Protein IsoformsABSTRACT
Elevated levels of lipoprotein(a) has been regarded as an independent risk factor for coronary, peripheral and cerebral atherosclerosis. The enormous intra-personal variation in the plasma concentration of lipoprotein(a) is almost entirely controlled by the apolipoprotein(a) i.e. gene locus on the chromosome 6q 26-27. The apolipoprotein(a) molecule is highly polymorphic and is known to exist in multiple, genetically determined isoforms. These polymorphisms may be responsible for difference in promoter activity, variable size of apolipoprotein(a) and thereby variation in plasma lipoprotein(a) concentration. We studied the effect of two types of polymorphisms, (i) variation in length of the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream of AUG codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma lipoprotein(a) levels in North Indian population. The study group consisted of 88 angiographically assessed male coronary artery disease patients (age range 30-70 years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat polymorphism was analysed using polymerase chain reaction. In all, 8/11 pentanucleotide repeat isoforms were observed. Using SDS-agarose gel electrophoresis and immunoblotting isoforms having 12-50 Kringle-4 type 2 repeats were detected. Our study indicates a strong association of elevated plasma lipoprotein(a) concentration with coronary artery disease. An inverse correlation was seen between lipoprotein concentration and isoform size for both the pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms; statistically significant difference (p = 0.001) was, however, observed only for the later.
Subject(s)
Adult , Aged , Apolipoproteins A/genetics , Coronary Disease/ethnology , Humans , India/epidemiology , Lipoprotein(a)/blood , Male , Middle Aged , Polymorphism, Genetic , Seroepidemiologic StudiesABSTRACT
Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.
Subject(s)
Female , Humans , Male , Apolipoprotein A-I/genetics , Apolipoproteins A/genetics , Apolipoproteins C/genetics , Apolipoproteins C/blood , Cholesterol/blood , Hypertriglyceridemia/genetics , Hypertriglyceridemia/complications , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/complications , Cholesterol, HDL/blood , Middle Aged , Multigene Family , Renal Dialysis , Triglycerides/blood , Genetic VariationABSTRACT
Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.