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Biomedical subjects

C F Xu

Publications and source records attributed to C F Xu.

At least 37 records · Page 2Linked to original sources
PubMed1994

Association between genetic variation at the APO AI-CIII-AIV gene cluster and familial combined hyperlipidaemia.

By using chemical cleavage mismatch analysis and the single strand conformation polymorphism technique, DNA fragments of the apo CIII gene, including the 5' flanking region and all the exons, were screened for sequence changes underlying the observed association between familial combined hyperlipidaemia (FCHL) and the apo AI-CIII-AIV gene cluster in affected individuals from eight FCHL families. A C1100-T transition in the wobble position of codon 14 in exon 3 and a T3206-G transversion in the non-translated region of exon 4 were identified, occurring in four and all probands, respectively. Using these variants and the G-75-A transition in the apo AI promoter, co-segregation of the gene cluster with hyperlipidaemia could be excluded in all eight families (lod score - infinity at theta = 0). No support for co-segregation was obtained using the affected pedigree member method of linkage analysis (overall T = -0.77 for f(p) = 1 [symbol: see text] p). The frequencies of T1100 and G3206 in a group of 55 patients with combined hyperlipidaemia were 0.35 and 0.52, respectively, which were significantly higher compared to 360 controls (0.21, p < 0.01 and 0.35, p < 0.005 respectively). In patients homozygous for the T1100 allele, levels of plasma triglyceride were 2.5-fold higher (868 mg/dl) than those homozygous for the C1100 allele (337 mg/dl), while patients heterozygous for the polymorphism had intermediate values (443 mg/dl) (p < 0.01). A similar association was seen in controls (p < 0.04). The three polymorphisms studied were in strong linkage disequilibrium in both the group of CHL patients and the unrelated individuals. This study confirms the association between common variation in the gene cluster and differences in plasma lipid levels in the general population and in patients with combined hyperlipidaemia, but fails to confirm co-segregation with FCHL, suggesting the role of other genetic or environmental factors in the aetiology of FCHL.

Adult↗
PubMed1994

The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase.

We have produced a detailed physical and transcriptional map of a 400 kb region within the narrowest flanking markers known to contain the hereditary breast and ovarian susceptibility gene, BRCA1. The approach described here has avoided the problems of chimaerism, instability and rearrangements commonly observed in yeast artificial chromosomes by converting the YAC clones into ordered chromosome 17-specific cosmid contigs and joining these contigs by cosmid end-walking. A detailed long-range restriction map provided a framework for the cosmid contig assembly and further refines existing physical mapping data. We have used a combined approach towards the isolation of the genes housed within these cosmids. This has resulted in the isolation and precise localisation of eight novel genes, including a novel G protein and an endogenous retrovirus related to the HERV-K family, and the previously described dual-specificity VHR phosphatase and MOX1 homeobox genes.

Animals↗
PubMed1994

[Changes of plasma motilin concentration in pregnancy and early postpartum period].

Plasma motilin concentration were determined by radioimmunoaction from 180 women during pregnancy and early postpartum period as compared with 20 healthy non-pregnant women. The results showed that mean plasma motilin concentration (384.40 +/- 110.30 ng/L) was higher in the first trimester of pregnancy than that of healthy non-pregnant women (366.12 +/- 96.23 ng/L), however, this difference did not reach statistical significance (P > 0.05). The mean plasma motilin concentration (323.90 +/- 125.10 ng/L) was lower in the second trimester of pregnancy than in the first trimester of pregnancy (P < 0.05), while the mean plasma motilin concentration in the third trimester of pregnancy (121.04 +/- 27.00 ng/L) was significantly lower than in second (P < 0.01) and the mean plasma motilin concentration in 3-5 d after delivery (443.05 +/- 140.79 ng/L) reached an even higher value (P < 0.01). Our results suggests that pregnancy appears to have a profound inhibitory effect on plasma motilin and this may in part be responsible for the gastrointestinal hypomotility during pregnancy.

Adult↗
PubMed1993

Role of genetic variation at the apo AI-CIII-AIV gene cluster in determining plasma apo AI levels in boys and girls.

We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (-75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8-11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II-CIII) and the apo CIII-AIV intergenic region (Pvu II-AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V-V+ of the G/A substitution and the PvuII-AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V-V-. In girls, however, there was evidence of significant interaction of effects between the PvuII-AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V+) of the PvuII-AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII-CIII and PvuII-AIV polymorphisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗
PubMed1993

[The frequencies of sister chromatid exchanges and chromosomal aberrations in the peripheral lymphocytes in patients with cervical carcinoma].

The study of the SCE frequencies and chromosome aberrations in 20 patients with cervical carcinoma and 20 cases of healthy women was carried out. The result showed that the SCE frequencies were as high as 9.28 +/- 0.34/cell in the patients with cervical cancer. They were significantly higher than those of the normal control group (P < 0.001). The chromosomal numerical changes and structural aberrations of the patients were much more than those of the normal women (P < 0.01). The important structural aberrations included ring chromosome, chromosomal restituation and breakage. Genetic instability and DNA repair level significantly suppressed in cancer patients were detected.

Adult↗
PubMed1993

[Effect of Equisetum hyemale on experimental hyperlipemia in rats and its toxic test].

The results of an experimental study in rats fed with Equisetum hyemale and hyperlipid food have proved that inhibiting effects on the elevation of triglyceride and cholesterol can be obviously observed in both high and low doses of Equisetum. The study also shows that Equisetum hyemale can antagonize the hyperlipemia in rats. The acute toxic test has proved its low toxicity.

Animals↗
PubMed1992

Dietary intake and gene variation influence the response of plasma lipids to dietary intervention.

We have examined whether variation at the apolipoprotein (apo) B, apo E, apo AII, and apo AI-CIII-AIV genes affected the relationship between dietary intake and serum lipid traits in individuals who had participated in dietary intervention from a basal high fat diet to a low fat diet followed by a return to their natural diet, the switchback. On both the basal and switchback diets where the variance of dietary intake was great, there was a significant correlation between P/S ratio and serum total, low-density lipoprotein (LDL) cholesterol, and apo AI levels. In addition dietary cholesterol (dchol) levels correlated significantly with serum apo AI levels on the basal diet. Comparing the difference between basal and intervention (delta 1) and between switchback and intervention diets (delta 2), changes in dchol and P/S ratio correlated significantly with changes in serum total, high-density lipoprotein (HDL) and LDL cholesterol, and apo B levels. There was a significant correlation between monounsaturated fatty acid (MUFA) and apo AI levels during both changes. Furthermore we have examined whether the relationship between variables was homogeneous among genotypes of candidate gene polymorphisms. A heterogeneous effect (P less than 0.01) was seen among genotypes of the PvuII-AIV restriction fragment length polymorphism (RFLP) on the correlation of serum LDL cholesterol levels and dietary MUFA during both dietary changes (delta 1 and delta 2). A heterogeneous effect among genotypes of the apo B XbaI RFLP on the correlation between dchol versus total and LDL cholesterol during the change delta 1, but not delta 2, was observed. Thus our results show that both dietary components and genetic variation affect the response of serum lipid, lipoprotein, and apolipoprotein levels to dietary change.

Adult↗
PubMed1992

DNA polymorphism studies. Approaches to elucidating multifactorial ischaemic heart disease: the apo B gene as an example.

It is well established that elevated plasma levels of low-density lipoprotein (LDL) particles are a risk factor for ischaemic heart disease with the distribution in LDL levels seen in the general population being the result of interaction between environmental factors, such as dietary fat intake, and genetic variation that is present in different individuals. One of the candidate genes where such variation is likely to occur, is the gene coding for apolipoprotein B (apo B). Many studies have reported an association between a common polymorphism of the apo B gene, detected using the restriction enzyme XbaI, and differences in plasma lipid levels, explaining 3-5% of the variance in LDL-cholesterol levels in samples representative of the healthy population. It has been proposed that the mechanism of this association is due to functional amino acid changes within the apo B protein, that affect LDL catabolism by altering binding affinity to the LDL-receptor. Several amino acid substitutions in the apo B gene have now been characterized, and these form the basis of the different epitopes that create the Ag marker system. Previous studies have reported that the Ag(x) epitope is associated with lower plasma lipid levels, and until recently the molecular basis for this association has been unclear. We have determined that the Ag(x) epitope is associated with both a Pro-Leu2712, and Asn-Ser4311 substitution, with the Leu-Ser allele being associated with significantly lower levels of plasma lipids in a sample of healthy individuals from Sweden.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Two amino acid substitutions in apolipoprotein B are in complete allelic association with the antigen group (x/y) polymorphism: evidence for little recombination in the 3' end of the human gene.

We report the identification of an A-to-G base change, in exon 29 of the apolipoprotein B (apo B) gene, that results in the substitution of serine for asparagine at residue 4311 of mature apo B100. In a recent publication, Huang et al. have reported a C-to-T base change in exon 26 that causes the substitution of leucine for proline at residue 2712 of apo B. We have found complete linkage disequilibrium between the alleles at both these sites and an immunochemical polymorphism of LDL designated antigen group (x/y) (Ag(x/y)) in a sample of 118 Finnish individuals. This implies that either one of these substitutions--or both of them combined--could be the molecular basis of the Ag(x/y) antigenic determinants, with the allele encoding serine4311 plus leucine2712 representing the Ag(x) epitope, and that encoding asparagine4311 plus proline2712 the Ag(y) epitope. In a sample of 90 healthy Swedish individuals the Leu2712/Ser4311 allele is associated both with reduced serum levels of LDL-cholesterol and apo B and with raised levels of HDL. However, these differences are of smaller effect than those associated with the XbaI RFLP of the apo B gene in this sample. We have also genotyped 523 individuals from European, Asian, Chinese, and Afro-Caribbean populations and have found complete association between the sites encoding residues 2712 and 4311 in all of these samples, although there are large allele frequency differences between these populations. In addition, there is strong linkage disequilibrium with allelic association between the alleles of these sites and those of the XbaI RFLP in all the populations examined. Taken together, these data suggest that, since the divergence of the major ethnic groups, there has been little or no recombination in the 3' end of the human apo B gene.

Adult↗
PubMed1991

Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.

We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.

Alleles↗
PubMed1991

Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects.

We have found a novel apoE5 mutation, using isoelectric focusing (IEF), in two apparently unrelated French-Canadian subjects. Co-dominant inheritance was demonstrated in the family of the first proband, a healthy male subject. The presence of the apoE5 form was not associated with lipid abnormalities or cardiovascular disease in this family. The second proband was a hyperlipidemic female patient suffering from angina, with no informative relatives available for study. In both individuals, monoclonal antibody studies demonstrated that the mutation was associated with the loss of two overlapping epitopes at the amino terminus of the protein. Cysteamine treatment of the very low density lipoproteins indicated that the mutant apoE contained only one cysteine residue, suggesting that apoE3 was the parental form. Two-dimensional electrophoresis suggested that the mutated protein had a slightly lower molecular weight (by 1-2 kDa). However, DNA sequencing of the third exon of the apoE gene in both probands revealed a single G to A substitution at the 48th nucleotide, changing the amino acid at position 13 from glutamic acid to lysine. These results were confirmed by oligo melting experiments with allele-specific probes in relatives of the probands. The study of this apoE variant should provide additional insight into the structure-function relationship of apoE.

Adult↗
PubMed1991

[Small bowel transit time measured with native lactulose breath hydrogen test].

Native lactulose was used in breath hydrogen test (BHT) to detect small bowel transit time (SBTT) in normal persons (34 cases) and patients with functional diarrhea (24 cases) and functional constipation (12 cases). The mean SBTT was 80.6 +/- 28.3 min, 58.4 +/- 42.2 min and 104.2 +/- 21.0 min respectively. When the mean SBTT in the patient groups was compared with that in the normal group, there was statistically significant difference (P less than 0.05 and 0.01 respectively). The results showed that native lactulose produces hydrogen successfully (94.3%). Few side-effects were found, if a dose of 10g was used.

Adolescent↗
PubMed1990

Genetic variation at the apolipoprotein gene loci contribute to response of plasma lipids to dietary change.

Dietary intervention studies (from a low polyunsaturated/saturated fatty acid ratio P/S diet to a high P/S diet), carried out on a group of healthy individuals from North Karelia, Eastern Finland between 1981-1984, provided evidence that there may be a genetic component contributing to variation in response to dietary change. We have resampled blood from 107 individuals involved in the original studies and used Restriction Fragment Length Polymorphisms (RFLPs) to study the genetic contribution of variation at a number of candidate gene loci to the response to dietary change. The genes investigated in this study were the apolipoprotein (apo) genes: apo B, apo AII, apo E (protein polymorphism), apo AI-CIII-AIV gene cluster, and the LDL-receptor gene. On the basal diet the major effect of genotype on lipid traits was due to variation at the apo E gene locus; this protein polymorphism explained 14.6% of the phenotypic variance in LDL cholesterol levels and 12.7% of the phenotypic variance in total cholesterol levels. When switched to low fat high P/S diet, these effects of variation at the apo E gene locus on the phenotypic variation of LDL and total cholesterol levels disappeared. The major effect on the response to dietary change, delta, was seen on the difference in apo AI levels mediated by variation at the apo B gene locus (MspI RFLP) explaining 6.3% of the phenotypic variance in apo AI change. For the RFLPs of the apo AI-CII-AIV gene cluster, small but not significant differences on delta were found. Our results indicate that within the limits of the candidate genes studied, the major effects in response to dietary change was on apo AI levels mediated through variation at the apo B gene locus.

Adult↗
PubMed1990

XbaI polymorphism of the apolipoprotein B gene influences plasma lipid response to diet intervention.

Fresh blood samples were collected from 103 North Karelians who had in 1981-84 participated in dietary intervention studies and analysis of the XbaI restriction fragment length polymorphism (RFLP) of apolipoprotein B (apoB) was carried out. Reanalysis of the original plasma lipid and apolipoprotein data indicated that while baseline concentrations did not differ significantly between genotypes, the response to a low-fat, low-cholesterol diet was influenced by apoB XbaI genotype: reductions in total and low density lipoprotein (LDL) cholesterol, apoB and high density lipoprotein (HDL) cholesterol were greater in subjects homo- or heterozygous for the presence of the XbaI cutting site (X1X2 or X2X2 genotype, designated X2+) as compared to those lacking the cutting site (X1X1 genotype, designated X2-). The corresponding average reductions induced by dietary intervention in X2+ and X2- subjects were: for total cholesterol 1.30 and 0.99 mmol/l (p = 0.036), for LDL cholesterol 1.04 and 0.78 mmol/l (p = 0.049), for apoB 18.3 and 8.1 mg/100 ml (p = 0.012) and for HDL cholesterol 0.26 and 0.17 mmol/l (p = 0.008).

Adult↗
PubMed1990

Apolipoprotein B signal peptide insertion/deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels.

We have investigated the insertion/deletion polymorphism in the signal peptide region of the apoB gene in 106 Finnish individuals from North Karelia. The relative frequency of the insertion allele in this sample was 0.73. Strong linkage disequilibrium was detected between this apoB insertion/deletion polymorphism and the Ag(c/g) epitope pair of apoB, while weak linkage disequilibrium was detected between the polymorphism and the four other reported Ag epitope pairs [(a1/d), (x/y), (h/i) and (t/z)], as well as the apoB PvuII and the XbaI RFLPs. Using one-way analysis of variance there was a statistically significant association (P less than 0.05) between the apoB insertion/deletion polymorphism and serum triglyceride levels in this sample. Individuals homozygous for the insertion allele had higher triglyceride levels than individuals homozygous for the deletion allele, while individuals heterozygous for the polymorphism had intermediate levels. These differences were reduced when individuals were consuming a low fat diet but were statistically significant when the individuals returned to their normal diet. It is possible that insertion or deletion of three hydrophobic amino acids (leu-ala-leu) from the signal peptide of apoB may have a direct effect on plasma triglyceride levels by altering the intracellular processing of apoB or apoB-containing lipoproteins in the liver or intestine.

Adult↗
PubMed1990

Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene loci is associated with lipoprotein and apolipoprotein levels in Italian children.

We have used RFLPs of the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene cluster to estimate the genetic contribution of variation at these loci to the variability of plasmid lipid, lipoprotein, and apolipoprotein levels in 209 children from Sezze in central Italy. The sample was randomly divided into group I (107 children) and group II (102 children). Four site polymorphisms (PvuII, XbaI, MspI, and EcoRI) of the apo B gene and five site polymorphisms (XmnI, PstI, SstI, PvuII-CIII, and PvuII-AIV) of the apo AI-CIII-AIV gene cluster were examined in group I children. After adjustment for gender, age, and body-mass index, polymorphisms at both gene loci (PvuII-B, PvuII-CIII, and PvuII-AIV) were associated with significant effects on the levels of plasma apo AI, apo B, or high-density lipoprotein-cholesterol. RFLPs that showed significant effects in group I were genotyped in group II. All three polymorphisms were associated with similar effects on apolipoprotein levels, though for all RFLPs the magnitude of the effects was smaller in the group II children and only statistically significant for the effect of the PvuII-B genotype on apo AI levels. In the total sample of 209 children 7.4% of the sample variance in apo AI levels was explained by variation associated with the apo B PvuII-B RFLP. In addition, the PvuII-B RFLP was associated with significant effects on plasma apo B levels and explained 5.7% of the sample variance. The PvuII-CIII and PvuII-AIV polymorphisms were both associated with differences in apo AI levels, explaining 3.7%-5.7% of the sample variance. Taken together, the three PvuII polymorphisms explained 17.7% of the phenotypic variance in apo AI levels. There was significant evidence for an effect of nonlinearity of the PvuII-CIII genotypes on apo AI levels, with the individuals heterozygous for the polymorphism having the highest apo AI levels. No evidence of interaction between genotype and gender, age, and body-mass index was shown by covariance analysis. The molecular explanation of this effect is unclear. Our data show that variation at both the apo AI-CIII-AIV and apo B loci are associated with lipoprotein and apolipoprotein levels in this sample of Italian children.

Alleles↗
PubMed1989

Apolipoprotein B amino acid 3611 substitution from arginine to glutamine creates the Ag (h/i) epitope: the polymorphism is not associated with differences in serum cholesterol and apolipoprotein B levels.

A G- to A-DNA sequence change in exon 26 of the human apolipoprotein B (apo B) gene leads to a glutamine substitution for arginine at codon 3611 of the mature apolipo-protein B100 and causes a loss of an MspI site. In 106 Finnish individuals, a complete correspondence exists between this MspI polymorphic site and the Ag (h/i) immunochemical polymorphism. Linkage disequilibrium was found between this MspI polymorphic site and the apo B XbaI and EcoRI variable sites and the Ag (al/d) and (c/g) epitope pairs; there is apparent linkage equilibrium with the apo B PvuII variable site. Based on three population studies (samples from London. Finland and Italy), no significant association was found between this RFLP and serum cholesterol and apo B levels. These data suggest that the arginine 3611----glutamine 3611 substitution has no significant effect on apo B function.

Adult↗