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

OBJECTIVEThe aim of this study was to investigate variations of apolipoprotein A IV (apo A IV) gene and its relation to endogenous hypertriglyceridemia(HTG) in Chinese population.

METHODSOne hundred and six endogenous hypertriglyceridemics and 171 healthy subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphisms (RFLPs) and sequencing of apoA IV gene amplified by polymerase chain reaction (PCR). The polymorphic sites of apo A IV gene studied included codon 9 (A to G, synonymous mutation), codon 347 (A to T, non-synonymous mutation), codon 360 (G to T, non-synonymous mutation), and Msp I polymorphism (CC/TGG) within intron 2.

RESULTSThe frequency of G allele at codon 9 in HTG group was higher than that in healthy controls(0.453 vs 0.366, P<0.05). The other polymorphic sites showed no significant differences of the allele frequencies between the two groups. The frequencies of rare alleles, such as G allele at codon 9, T allele at codon 347 and T allele at codon 360 polymorphic site were significantly different from those reported in European Caucasians (0.366 vs 0.032, P<0.001, 0.000 vs 0.160, P<0.001; 0.000 vs 0.070, P<0.001), but no differences were found when compared with those in Japanese, including Msp I site (P>0.05). In the healthy male control group, subjects with genotype G/G of codon 9 had a higher serum mean concentration of apoA I when compared with that of genotype A/A(P<0.01). In the HTG group, subjects with genotype C/T of Msp I site had a higher serum mean concentration of TG with compared with those with genotype C/C and T/T (P<0.05). This difference was only observed in male HTG group when male and female subgroups were further separated.

CONCLUSIONThese results suggest that Msp I and codon 9 polymorphism in apoA IV gene are associated with endogenous hypertriglyceridemia to some extent in Chinese population.

Adult ; Amino Acid Sequence ; Apolipoproteins A ; genetics ; Base Sequence ; China ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Female ; Genetic Variation ; Humans ; Hypertriglyceridemia ; genetics ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length

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 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 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

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.
Apolipoprotein A-I/genetics* ; Apolipoproteins A/genetics* ; Apolipoproteins C/genetics* ; Apolipoproteins C/blood ; Cholesterol/blood ; Female ; Human ; Hypertriglyceridemia/genetics* ; Hypertriglyceridemia/complications ; Kidney Failure, Chronic/genetics* ; Kidney Failure, Chronic/complications ; Lipoproteins, HDL Cholesterol/blood ; Male ; Middle Age ; Multigene Family* ; Renal Dialysis ; Triglycerides/blood ; Variation (Genetics)*

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.
Apolipoprotein A-I/genetics* ; Apolipoproteins A/genetics* ; Apolipoproteins C/genetics* ; Apolipoproteins C/blood ; Cholesterol/blood ; Female ; Human ; Hypertriglyceridemia/genetics* ; Hypertriglyceridemia/complications ; Kidney Failure, Chronic/genetics* ; Kidney Failure, Chronic/complications ; Lipoproteins, HDL Cholesterol/blood ; Male ; Middle Age ; Multigene Family* ; Renal Dialysis ; Triglycerides/blood ; Variation (Genetics)*

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*

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 polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD.

METHODSGenomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high-performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method.

RESULTSA novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi-square test showed no significant difference in the frequencies of the A/A genotype and A allele (P > 0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P < 0.05).

CONCLUSIONNo direct association was found between the LPL Arg192-->Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.

Alleles ; Apolipoproteins ; blood ; Cholesterol, HDL ; blood ; Chromatography, High Pressure Liquid ; methods ; Coronary Disease ; blood ; enzymology ; genetics ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Gene Frequency ; Humans ; Hypertriglyceridemia ; blood ; genetics ; Lipoprotein Lipase ; genetics ; Lipoproteins ; blood ; Polymorphism, Genetic