As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet β cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body's energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent "contributor" to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet β cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet β cell function, and the underlying mechanism remains to be further discussed.
Apolipoprotein C-III/genetics* ; Non-alcoholic Fatty Liver Disease/pathology* ; Glucose/metabolism* ; Lipid Metabolism ; Humans ; Animals ; Hypertriglyceridemia/metabolism* ; Islets of Langerhans/metabolism*

Humans ; Comorbidity ; Diabetes Mellitus/genetics* ; East Asian People ; Hypertension/genetics* ; Hypertriglyceridemia/genetics* ; Obesity/genetics* ; Receptors, Calcitriol/genetics*

OBJECTIVETo investigate the association of ten SNP at peroxisome proliferator-activated receptors (PPARα, δ, γ) with hypertriglyceridemia and the gene-gene interaction.

METHODSParticipants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu province of China Study (PMMJS). A total of 820 subjects were selected from the 4083 participants who had received follow-up examination, by using simple random sampling. Participants in baseline and follow-up study surveys were both collected blood samples 11 ml in the morning after at least 8 hours of fasting. Blood samples which collected at the baseline were subjected to PPARα, PPARδ and PPARγ genotype analyses. Blood samples which collected at the follow-up were used to measure serum triglyceride levels. The logistic regression model was used to analyze the association between different SNP and hypertriglyceridemia, and the generalized multifactor dimensionality reduction (GMDR) was applied to explore the gene-gene interaction.

RESULTSThe samples included 474 in the non-hypertriglyceridemia group and 346 in the hypertriglyceridemia group. The genotype frequencies of rs1800206 in the hypertriglyceridemia group were 211 (61.0%) for LL, 132 (38.2%) for LV and 3 (0.9%) for VV, and in the non-hypertriglyceridemia group were 411 (86.7%) for LL, 59 (12.4%) for LV and 4(0.8%) for VV (χ(2) = 74.18, P < 0.01). V allele frequencies of rs1800206 in the hypertriglyceridemia group was 138(19.9%), and in the non-hypertriglyceridemia group was 67 (7.1%) (χ(2) = 60.62, P < 0.01). The genotype frequencies of rs2016520 in the hypertriglyceridemia group were 177 (51.2%) for TT, 154 (44.5%) for TC and 15 (4.3%) for CC, and in the non-hypertriglyceridemia group were 211 (44.5%) for TT, 212 (44.7%) for TC and 51 (10.8%) for CC(χ(2) = 15.93, P < 0.01). C allele frequencies of rs2016520 in the hypertriglyceridemia group was 184(26.6%), and in the non-hypertriglyceridemia group was 314 (33.1%) (χ(2) = 8.07, P < 0.01). The genotype frequencies of rs3856806 in the hypertriglyceridemia group were 149 (43.1%) for CC, 156 (45.1%) for CT and 41 (11.8%) for TT, and in the non-hypertriglyceridemia group were 269 (56.8%) for CC, 170 (35.9%) for CT and 35 (7.4%) for TT (χ(2) = 15.93, P < 0.01). T allele frequencies of rs3856806 in the hypertriglyceridemia group was 238(34.4%), and was 240 (25.3%) in the non-hypertriglyceridemia group (χ(2) = 15.96, P < 0.01). The genotype frequencies of rs1805192 in the hypertriglyceridemia group were 145 (41.9%) for PP, 158(45.7%) for PA and 43(12.4%) for AA, and in the non-hypertriglyceridemia group were 314 (66.2%) for PP, 137(28.9%) for PA and 23(4.9%) for AA (χ(2) = 50.92, P < 0.01). A allele frequencies of rs1805192 in the hypertriglyceridemia group was 244(35.2%), and was 183 (19.3%) in the non-hypertriglyceridemia group(χ(2) = 52.89, P < 0.01). After adjusting age, gender, smoking, alcohol consumption, high-fat diet, low -fiber diet and occupational physical activity factors, rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceride, while the OR (95%CI) was 3.88 (2.69 - 5.60), 0.71 (0.52 - 0.96), 1.40 (1.03 - 1.90) and 2.56 (1.88 - 3.49), respectively (P < 0.05). GMDR model analysis showed that the second-order model (rs1800206 and rs1805192) was the best model when quality traits of triglyceride was chosen as outcome (P < 0.01); while third-order model (rs1800206, rs1805192 and rs2016520) was the best model when quantitative traits of triglyceride was chosen as outcome (P < 0.01).

CONCLUSIONThe rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia. There was a gene-gene interaction between multiple SNP.

Adult ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; blood ; genetics ; Logistic Models ; Male ; Middle Aged ; Peroxisome Proliferator-Activated Receptors ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the polymorphism of acyl-coenzyme A: cholesterol acyltransferase 1(ACAT1) gene and its relationship with endogenous hypertriglyceridemia (HTG) in Chinese population.

METHODSA total of three hundred and seventy-two subjects (105 endogenous hypertriglyceridemics and 267 healthy controls) from a population of Chinese Han nationality in Chengdu area were studied using PCR-restriction fragment length polymorphism (RFLP).

RESULTSThe frequency of C allele in normal Chinese at rs1044925 locus was 0.137, which was lower than that reported in the population of central and Southern Europe (0.354) (P< 0.05). The frequency C allele was 0.153 in HTG group. No significant difference between normal control and HTG group. In control group, subjects with genotype AA had a higher serum mean concentrations of low density lipoprotein-cholesterol (LDL-C) and non-high density lipoprotein-cholesterol(nHDL-C) when compared with those of C allele carriers (AC and CC genotype carriers), respectively [(3.25+/- 0.68) mmol/L vs (3.03+/- 0.87) mmol/L, P< 0.05; (3.80+/- 0.71) mmol/L vs (3.23+/- 0.82) mmol/L, P< 0.05]. In HTG group, subjects with genotype AA had a higher high density lipoprotein-cholesterol (HDL-C) level compared with those of C allele carriers [(1.00+/- 0.28) mmol/L vs (0.87+/- 0.17) mmol/L, P< 0.05].

CONCLUSIONThese results suggest that rs1044925 polymorphism in ACAT1 gene is not only associated with serum LDL-C and nHDLC levels in healthy Chinese subjects in Chengdu area, but also with HDL-C level in subjects with endogenous hypertriglyceridemia in this population.

Adult ; Aged ; Asian Continental Ancestry Group ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Sterol O-Acyltransferase ; genetics ; Young Adult

OBJECTIVETo investigate the Arg16Gly polymorphism of beta2-adrenergic receptor (beta2AR) gene and its association with endogenous hypertriglyceridemia (HTG) in Chinese population.

METHODSThree hundred and forty one subjects including 100 HTG patients and 241 healthy controls from a population of Chinese Han nationality in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs).

RESULTSThe frequencies of Gly allele at the Arg16Gly locus in combined group was 0.446, and were 0.427 and 0.490 in normal and HTG group, respectively. No significant difference was found in both allele and genotype frequencies between normal control and HTG group. The frequency of Gly allele at the Arg16Gly locus in beta2-adrenergic receptor gene in the population (0.446) was similar to that of Japanese (0.505), higher than that of American white(0.248), and lower than that of Polish population (0.633). In normal controls, subjects with genotype Arg/Arg had a higher concentration of serum TG and apoB100, and lower apoAII levels, when compared with those with genotypes Arg/Gly or Gly/Gly, respectively (vs. Arg/Gly for TG, vs. Gly/Gly for apoB100 and apoAII, respectively, P<0.05). In HTG group, subjects with genotype Arg/Arg had higher serum TC and low-density lipoprotein cholesterol levels when compared with those with Gly/Gly genotype (5.36+/-0.74 mmol/L vs. 4.77+/-1.07 mmol/L,P<0.05;3.03+/-0.70 mmol/L vs. 2.38+/-1.10 mmol/L,P<0.05).

CONCLUSIONThese results suggest that the Arg16Gly polymorphism in beta2-adrenergic receptor gene are not only associated with serum TG,apoB100 and apoAII levels in the healthy Chinese subjects in Chengdu area, but also with serum TC and low-density lipoprotein cholesterol levels in subjects with endogenous hypertriglyceridemia. The Arg16Gly polymorphism in beta2-adrenergic receptor gene may be associated with TG and/or cholesterol metabolism in Chinese Han population.

Adult ; Aged ; Apolipoprotein B-100 ; blood ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; blood ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Adrenergic, beta-2 ; genetics ; Triglycerides ; blood

OBJECTIVETo explore the relationship of apolipoprotein E (ApoE) genotype with hypertriglyceridemia-associated recurrent acute pancreatitis.

METHODSTaking the fasting serum triglyceride (TG) level > or = 2.3 mmol/L as hypertriglyceridemia, ApoE genotypes in 115 patients with hypertriglyceridemia-associated recurrent acute pancreatitis were assessed by polymerase chain reaction. According to the fasting serum TG level, all patients were divided into 3 groups: TG mild elevation group (2.3 mmol/L < or = TG < 5.5 mmol/L, Group A), TG moderate elevation group (5.5 mmol/L < or = TG < 11.3 mmol/L, Group B), and TG severe elevation group (TG > or = 11.3 mmol/L, Group C).

RESULTSGroup C had significantly fewer patients with biliary tract disease, improper diet and heavy alcohol consumption, and significantly more patients with passed history of moderate-severe hypertriglyceridemia than Group A and B (P < 0.05). The proportion of patients with E3/4, E3/2, E2/4 and E2/2 genotypes and gene frequency for epsilon 2 and epsilon 4 alleles are significantly higher in Group C than in Group A and B(P < 0.05). Group B had significantly more patients with E3/2 genotype and higher gene frequency for epsilon 2 allele than Group A (P < 0.05).

CONCLUSIONSApo epsilon 2 and epsilon 4 alleles are closely related to moderate-severe hypertriglyceridemia-associated recurrent acute pancreatitis.

Acute Disease ; Adolescent ; Adult ; Alleles ; Apolipoproteins E ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; complications ; Male ; Middle Aged ; Pancreatitis ; complications ; genetics ; Recurrence

OBJECTIVETo investigate the effects of the -384A>C polymorphism in the promoter region of endothelial lipase (EL) gene on serum lipid and apolipoprotein levels in healthy normolipidemic (HTG) and endogenous hypertriglyceridemic (HTG) subjects.

METHODSTwo hundred and fourteen healthy normolipidemic and 103 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the radial immunadiffussion kits.

RESULTSThe frequency of the C allele at the -384A>C site in EL gene in the population (0.178) was higher than that of Japanese population (0.119) and Japanese Americans (0.115) (P < 0.01 and P < 0.01), respectively. No significant difference between normolipidemic and HTG groups was found in both allele and genotype frequencies. In normal group, subjects of the C allele carriers (A/C and C/C genotype carriers) had a higher serum mean concentration of TC, LDL-C and nHDL-C when compared with those of genotype AA (5.23 +/- 0.74 mmol/L vs 4.93 +/- 0.74 mmol/L, P=0.025; 3.27 +/- 0.74 mmol/L vs 2.98 +/- 0.80 mmol/L, P=0.038; 3.81 +/- 0.73 mmol/L vs 3.49 +/- 0.85 mmol/L, P=0.031, respectively). Similar result was only observed in female subgroup when male and female subgroups were further separated. No significant changes of lipid and lipoprotein levels were observed in the polymorphism in HTG group.

CONCLUSIONThese results suggest that the -384A>C polymorphism in the promoter region of the endothelial lipase gene is associated with serum TC, LDL-C, and nHDL-C levels in healthy Chinese subjects in Chengdu area, but not associated with the lipid levels in the endogenous hypertriglyceridmic group.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Apolipoproteins C ; genetics ; Asian Continental Ancestry Group ; genetics ; Female ; Gene Frequency ; Humans ; Hypertriglyceridemia ; genetics ; Lipase ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Population Groups ; genetics ; Promoter Regions, Genetic ; genetics ; Triglycerides ; blood ; Young Adult

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.
Apolipoproteins A/*genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; *Haplotypes ; Humans ; Hypertriglyceridemia/genetics ; Korea ; Linkage Disequilibrium ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Triglycerides/*blood

OBJECTIVETo investigate the cholesterol 7alpha-hydroxylase gene -204A/C polymorphism and its relationship with serum lipids and apolipoproteins (apo) levels in patients with endogenous hypertriglyceridemia (HTG) in Chinese population in Chengdu area.

METHODSThe genotype and allele frequencies of cholesterol 7alpha-hydroxylase gene -204A/C polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the RID kits in 132 HTG patients and 212 control subjects.

RESULTSAllele frequencies of A and C were 0.602 and 0.398 in HTG group and 0.601 and 0.399 in control group, respectively. There was no significant difference of allele and genotypes frequencies between HTG and control groups (P> 0.05). In HTG group, carriers with the genotypes CC and AC were associated with significantly higher concentrations of triglycerides and apoCIII compared with those with genotype AA (P< 0.05). In the control group, carriers with the genotypes CC and AC were associated with significantly lower serum high density lipoprotein cholesterol (HDL-C) level compared with those with genotype AA (P< 0.05). In the male control group, carriers with the genotypes CC and AC had elevated levels of serum triglycerides than those with genotype AA (P< 0.05).

CONCLUSIONThese results suggest that -204A/C polymorphism in the CYP7A1 gene does not relate with HTG but may has an effect on serum triglyceride and apoCIII levels in patients with endogenous HTG, the serum HDL-C level in control subjects and the serum TG level in male control subjects.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Cholesterol 7-alpha-Hydroxylase ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; blood ; ethnology ; genetics ; Lipids ; blood ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length

OBJECTIVETo investigate the variations of ATP binding cassette A1 (ABCA1) gene and its relation to endogenous hypertriglyceridemia (HTG) in Chinese population.

METHODSA total of three hundred and nine subjects (one hundred and nine endogenous hypertriglyceridemics and 200 healthy controls) from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLP) amplified by polymerase chain reaction (PCR).

RESULTSThe frequency of K allele at R219K site 0.472 and 0.436 in normal and HTG group, respectively. No significant difference between normal control and HTG group was found in both allele and genotype frequencies. In both normal and HTG groups, subjects with genotype KK had a higher serum mean concentration of high density lipoprotein-cholesterol (HDL-C) when compared with those with genotype RR, respectively (1.48+/-0.45 mmol/L vs 1.27+/-0.29 mmol/L, P<0.05; 1.07+/-0.30 mmol/L vs 0.87+/-0.19 mmol/L, P<0.05). In normal group, subjects with genotype RK had a lower triglyceride (TG) level compared with those with genotype RR (1.22+/-0.37 mmol/L vs 1.41+/-0.84 mmol/L, P<0.05). In addition, the subjects carrying K allele in HTG group had a decreased total cholesterol (TC)/HDL-C ratio compared with those with genotype RR (KK vs RK vs RR: 4.82+/-1.28 vs 5.42+/-1.62 vs 6.33+/-1.70, P<0.05).

CONCLUSIONThese results suggest that R219K polymorphism in ABCA1 gene is not only associated with serum HDL-C and TG levels in healthy Chinese subjects in Chengdu area, but also with HDL-C level and TC/HDL-C ratio in subjects with endogenous HTG.

ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; genetics ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; China ; Cholesterol, HDL ; blood ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Hypertriglyceridemia ; blood ; ethnology ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Triglycerides ; blood