Biomedical subjects

Ping An

Publications and source records attributed to Ping An.

54 records · Page 3Linked to original sources

PubMed2003

Identification of antigens by monoclonal antibody PD4 and its expression in Escherichia coli.

AIM: To clone and express the antigen of monoclonal antibody (MAb) PD4 for further investigation of its function. METHODS: MGC803 cDNA expression library was constructed and screened with PD4 as probes to clone the antigen. After failed in the library screening, immunoprecipitation and SDS-polyacrylamide gel electrophoresis were applied to purify the antigen for sequence analysis. The antigen coming from Mycoplasma hyorhinis (M. hyorhinis) was further confirmed with Western blot analysis by infecting M. hyorhinis -free HeLa cells and eliminating the M. hyorhinis from MGC803 cells. The full p37 gene was cloned by PCR and expressed successfully in Escherichia coli after site-directed mutations. Immunofluorescence assay was used to demonstrate if p37 protein could directly bind to gastric tumor cell AGS. RESULTS: The cDNA library constructed with MGC803 cells was screened by MAb PD4 as probes. Unfortunately, the positive clones identified with MAb PD4 were also reacted with unrelated antibodies. Then, immunoprecipitation was performed and the purified antigen was identified to be a membrane protein of Mycoplasma hyorhinis (M. hyorhinis) by sequencing of N-terminal amino acid residues. The membrane protein was intensively verified with Western blot by eliminating M. hyorhinis from MGC803 cells and by infecting M. hyorhinis-free HeLa cells. The full p37 gene was cloned and expressed successfully in Escherichia coli after site-directed mutations. Immunofluorescence demonstrated that p37 protein could directly bind to gastric tumor cell AGS. CONCLUSION: The antigen recognized by MAb PD4 is from M. hyorhinis, which suggests the actions involved in MAb PD4 is possibly mediated by p37 protein or M. hyorhinis. As p37 protein can bind directly to tumor cells, the pathogenic role of p37 involved in tumorigenesis justifies further investigation.

Antibodies, Monoclonal↗

PubMed2003

[Experimental study of total nutrient admixture promoting transfection of plasmid DNA mediated with liposomes to colorectal cancer cells].

OBJECTIVE: To study total nutrient admixture (TNA) promoting plasmid DNA transfection mediated with liposomes to colorectal cancer cells. METHODS: Dispensing varied transfection agents of liposome + DNA plasmid pEGFP-N(1), TNA + liposomes + pEGFP-N(1), TNA + pEGFP-N(1), liposomes merely, and TAN sole. Human colorectal cancer cell LoVo and HR-8348 were treated with the agents respectively. Green fluorescence protein (GFP) gene as a report gene was detected. RESULTS: GFP was not detected in cancer cells treated with agents of merely liposomes and TAN. Transfection rates of GFP in two groups of cancer cells treated with agent of TNA + liposomes + pEGFP-N(1) were 33%, 38% respectively. With liposome + pEGFP-N(1), the rates of transfection in two cells were 22%, 24% respectively. The expression of GFP was 1% in the two groups of tumor cells treated with TNA + pEGFP-N(1). With agent of TNA + liposomes + pEGFP-N(1), a high transfection rate of GFP gene was obtained. And no negative effect was observed to stabilization of TAN solution. CONCLUSION: TNA may enhance transfection rate of plasmid DNA mediated with liposome, and may be beneficial to the treatment of cancer.

Colorectal Neoplasms↗

PubMed2003

[The influence of FasL gene expression upon hepatic metastasis of colorectal carcinoma].

OBJECTIVE: To study FasL gene expression in colorectal carcinoma and its influences on biological behaviour of colorectal cancer and hepatic metastasis. METHODS: FasL gene expressions were examined with RT-PCR technique in the primary locus of colorectal cancer, mucosa adjacent to cancer, and hepatic metastasis. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rates and cell response to 5-FU and carboplatin were observed and analysed with MTT method. RESULTS: FasL gene expressions were detected in the primary site of colorectal cancer (n = 58), cancer adjacent mucosa (n = 58), and hepatic metastasis (n = 28). The positive rate of FasL expression was 24% (14/58), 14% (8/58), 100% (28/28), respectively, in primary site, tumor adjacent mucoca and hepatic metastasis. FasL expression rate in hepatic metastasis was higher than that in the primary site (chi2 = 43.49, P < 0.01) and tumor adjacent mucosa (chi2 = 57.66, P < 0.01). In a group of patients with hepatic metastasis, FasL expression rate in primary site was higher than that in patients without hepatic metastasis (chi2 = 3.96, P < 0.05). In vitro experiment, positive expression of FasL was found in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and control cancer cells (t = 9.02, t = 11.93, P < 0.01). Under same concentration of chemotheraputic agent, survival rate of FasL positive HR-8348 cells was higher than that of control cells. CONCLUSIONS: FasL positive cancer cells have more powerful resistance to chemotheraputic drugs. Expression of FasL gene in colorectal cancer cells is related with immune evasion to escape killing by immune cells, showing stronger drug-resistance, and it facilitates hepatic metastasis.

Adult↗

PubMed2002

Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study.

A genome-wide linkage scan was performed for genes affecting submaximal exercise cardiac output (Q) and stroke volume (SV) in the sedentary state and their responses to a standardized 20-wk endurance training program. A total of 509 polymorphic markers were used, and 328 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available. Q and SV were measured in relative steady state during exercise at 50 W (Q50 and SV50, respectively). Baseline phenotypes were adjusted for age, sex, and body surface area (BSA), and the training responses (post-training - baseline, Delta) were adjusted for age, sex, baseline BSA, and baseline value of the phenotype. Three analytical strategies were used: a multipoint variance components linkage analysis using all the family data, and regression-based single- and multipoint linkage analyses using pairs of siblings. In whites, baseline SV50 and DeltaSV50 showed promising linkages (P < 0.0023) with markers on chromosomes 14q31.1 and 10p11.2, respectively. Suggestive evidence of linkage (0.01 > P > 0.0023) for DeltaSV50 and Delta Q50 was detected on chromosome 2q31.1 and for baseline SV50 and Q50 on chromosome 9q32-q33. In blacks, markers on 18q11.2 showed promising linkages with baseline Q50. Suggestive evidence of linkage was found in three regions for baseline SV50 (1p21.3, 3q13.3, 12q13.2) and one for baseline SV50 and Q50 (10p14). All these chromosomal regions include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies.

Adult↗

PubMed2002

Modulating influence on HIV/AIDS by interacting RANTES gene variants.

RANTES (regulated on activation normal T cell expressed and secreted), a ligand for the CC chemokine receptor 5, potently inhibits HIV-1 replication in vitro. We tested the influence of four RANTES single nucleotide polymorphism (SNP) variants and their haplotypes on HIV-1 infection and AIDS progression in five AIDS cohorts. Three SNPs in the RANTES gene region on chromosome 17 (403A in the promoter, In1.1C in the first intron, and 3'222C in the 3' untranslated region) are associated with increased frequency of HIV-1 infection. The common In1.1C SNP allele is nested within an intronic regulatory sequence element that exhibits differential allele binding to nuclear proteins and a down-regulation of gene transcription. The In1.1C allele or haplotypes that include In1.1C display a strong dominant association with rapid progression to AIDS among HIV-1-infected individuals in African-American, European-American, and combined cohorts. The principal RANTES SNP genetic influence on AIDS progression derives from the down-regulating RANTES In1.1C allele, although linkage disequilibrium with adjoining RANTES SNPs including a weaker up-regulating RANTES promoter allele (-28G), can modify the observed epidemiological patterns. The In1.1C-bearing genotypes account for 37% of the attributable risk for rapid progression among African Americans and may also be an important influence on AIDS progression in Africa. The diminished transcription of RANTES afforded by the In1.1C regulatory allele is consistent with increased HIV-1 spread in vivo, leading to accelerated progression to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis.

Rheumatoid arthritis is a prevalent example of an inflammatory angiogenic disease, which is mediated by pro-inflammatory and pro-angiogenic cytokines such as tumor necrosis factor (TNF). To evaluate the effect of the potent anti-angiogenic factor endostatin on TNF-induced inflammatory arthritis, we injected an endostatin-expressing lentiviral vector directly into the joints of human TNF-transgenic mice before the onset of disease. Histological analysis of the injected joints 8 weeks later revealed that endostatin reduced blood vessel density within the synovial tissues and an overall mean arthritis index. In vitro and in vivo examination of the potential mechanism by which endostatin inhibited the arthritis revealed that endostatin blocks TNF-induced activation of JNK and JNK-dependent pro-angiogenic gene expression. These data suggest a novel mechanism by which endostatin inhibits angiogenesis, and demonstrates the potential utility of anti-angiogenic gene therapy for treatment of inflammatory arthritis.

Angiogenesis Inhibitors↗

PubMed2002

A genetic study of cortisol measured before and after endurance training: the HERITAGE Family Study.

The aim of this study was to investigate whether there are familial influences on cortisol levels at baseline and in response to endurance exercise training and, if so, whether there is evidence for a major gene effect. There were 476 white individuals in 99 nuclear families and 247 black individuals in 105 families with valid cortisol data in the HERITAGE Family Study. Data adjustments were carried out separately in each of 8 sex by generation by race groups, using stepwise multiple regression procedures. The familial factors underling the variability in baseline cortisol (log-transformed and adjusted for age and baseline body mass index [BMI]) and its training response (post-training minus baseline, adjusted for age, baseline BMI, and the baseline cortisol value) were assessed by estimating familial correlations and carrying out segregation analysis. In the white sample, significant familial resemblance was detected for both baseline cortisol and the training response, with maximal heritabilities of 38% and 32%, respectively. However, significant familial correlations were not detected for either cortisol phenotype in the black sample, perhaps owing, in part, to the much smaller family sizes. Results of segregation analysis of the white sample provided evidence for Mendelian additive genes influencing baseline cortisol and its training response. The major genes accounted for 33% and 31% of the variance for baseline cortisol and the training response with 48% and 5% of the sample homozygous for the genotype leading to high values, respectively. In conclusion, we found significant familial effects influencing levels of baseline cortisol and its training response in the white sample. The putative major gene effects appear to explain most of the observed familial resemblance, this will motivate further linkage and association studies.

Adolescent↗

PubMed2002

Heritability of HR and BP response to exercise training in the HERITAGE Family Study.

PURPOSE: The heritability of the response to exercise training in resting blood pressure (BP) and heart rate (HR) was assessed in 482 Caucasian individuals comprising 98 families participating in the HERITAGE Family Study. METHODS: All individuals were sedentary at the baseline visit (time 1 measurement). After completing a 20-wk exercise-training program, subjects were measured again (time 2). A familial correlation model was used to assess the heritability (genetic plus familial environmental) of the response in resting systolic BP (SBP), diastolic BP (DBP), and HR, computed as the difference between the two measurement times. This response was adjusted for the effects of baseline levels and age within sex and generation groups. Analyses were conducted separately in a subsample of families in which at least one family member was considered to have elevated BP (95th percentile; SBP > or = 135 or DBP > or = 80). RESULTS: Several novel findings emerged from this study. First, the SBP and HR response may be influenced by genetic factors. The maximal heritabilities were 20% (SBP) and 36% (HR) in the elevated BP, 18% and 24% in the complete, and not significant in the normotensive samples. For DBP, there were cohort effects (significant sibling and spouse but not parent-offspring correlations) in the complete and normotensive samples that may be due to generation-specific environmental influences. CONCLUSION: The trainability of SBP and HR in families with elevated BP appears to be determined in part by genetic factors, whereas DBP trainability may be more a function of environmental effects.

Adolescent↗

PubMed2002

Etk/Bmx as a tumor necrosis factor receptor type 2-specific kinase: role in endothelial cell migration and angiogenesis.

Tumor necrosis factor (TNF) is a cytokine that mediates many pathophysiologial processes, including angiogenesis. However, the molecular signaling involved in TNF-induced angiogenesis has not been determined. In this study, we examined the role of Etk/Bmx, an endothelial/epithelial tyrosine kinase involved in cell adhesion, migration, and survival in TNF-induced angiogenesis. We show that TNF activates Etk specifically through TNF receptor type 2 (TNFR2) as demonstrated by studies using a specific agonist to TNFR2 and TNFR2-deficient cells. Etk forms a preexisting complex with TNFR2 in a ligand-independent manner, and the association is through multiple domains (pleckstrin homology domain, TEC homology domain, and SH2 domain) of Etk and the C-terminal domain of TNFR2. The C-terminal 16-amino-acid residues of TNFR2 are critical for Etk association and activation, and this Etk-binding and activating motif in TNFR2 is not overlapped with the TNFR-associated factor type 2 (TRAF2)-binding sequence. Thus, TRAF2 is not involved in TNF-induced Etk activation, suggesting a novel mechanism for Etk activation by cytokine receptors. Moreover, a constitutively active form of Etk enhanced, whereas a dominant-negative Etk blocked, TNF-induced endothelial cell migration and tube formation. While most TNF actions have been attributed to TNFR1, our studies demonstrate that Etk is a TNFR2-specific kinase involved in TNF-induced angiogenic events.

Amino Acid Motifs↗

PubMed2002

[X-ray combined with cytosine deaminase suicide gene therapy enhances killing of colorectal carcinoma cells in vitro].

OBJECTIVE: To study the effect of X-ray on gene transfer and the antitumoral effect of X-ray combined with suicide gene therapy on colorectal carcinoma cells. METHODS: Green fluorescent protein (GFP) was seen under fluorescent microscope. GFP gene was used for reporting gene to learn gene transfer efficiency and gene expressing time under the influence of radiation. G418 was used to select cytosine deaminase (CD) positive neoplasm cells and CD gene transfer efficiency was tested by cloning efficiency. Antitumoral effect of X-ray combined with CD and 5-FC on colorectal carcinoma cells was tested by MTT. RESULTS: 4 Gy radiation could improve supercoiled plasmid DNA transfer efficiency for about 2 - 4 times and 30 times for linearized plasmid DNA. The mean durations of GFP gene expression treated with 4 Gy radiation were 14 d for supercoiled plasmid and 21 and for linearized plasmid, while in control group, the time was 12 d. Middle-dose radiation combined with CD and 5-FC could kill 99 percent of colorectal carcinoma cells, while in the control group, 5-FC only killed 15 percent of colorectal carcinoma cells which were transduced with CD gene. CONCLUSIONS: X-Ray combined with suicide gene therapy may be used as a promising method for treating colorectal neoplasm.

Antimetabolites↗

PubMed2002

[Expression of human mammaglobin mRNA in peripheral blood of breast cancer and their implication].

OBJECTIVE: To study the expression of human mammaglobin (hMAM) mRNA in the peripheral blood of breast cancer patients and its implication. METHODS: The expression of human mammaglobin mRNA was determined by using RT-PCR method in 56 patients with peripheral blood breast cancer, 8 patients with breast hyperplasia and 8 women with normal breast. The expression of hMAM mRNA was compared with biological significance and change of hMAM mRNA in chemotherapy after operation. RESULTS: The expression of hMAM mRNA was negative in 8 patients with breast hyperplasia, 8 women with normal breast and 56 patients with breast cancer, The positive rate was 30.4% (17/56) (chi(2) = 19.766, P < 0.01). The expression of hMAM mRNA in peripheral blood was not correlated with clinical stage, primary tumor size and patients age (chi(2) = 1.256, P > 0.05). After short-term large dose of chemotherapy, 41.2% (7/17) patients turned positive before operation to negative hMAM mRNA expression and negetive expression before operation positive expression after chemotherapy. CONCLUSIONS: This study suggests that hMAM is sensitive and specific for breast cancer. Detection of the expression of hMAM mRNA in peripheral blood of breast cancer is of value in the diagnosis and judgement of prognosis of breast cancer.

Adult↗

PubMed2002

[Three-pronged approach to treat rectal cancer: liposome transfer cytosine deaminase gene, ionizing radiation and dendritic cells].

OBJECTIVE: To investigate the anticancer activity of three-pronged approach: liposome transfer cytosine deaminase (CD) gene, ionizing radiation, and dendritic cells (DCs). METHODS: After rectal cancer cells were killed by CD and 5-FC and radiotherapy with improved liposome transfection and radiosensitization, the killed cancer cells, DCs and T lymphocytes were incubated together. The uptake of (3)H-TdR weighed the immune activity of DCs. The effect of anticancer was monitored by MTT. RESULTS: DCs acquired the apoptosis body and other antigen from the killed cancer cells and presented them to T-lymphocytes. The induced CTL killed the cancer cells powerfully and selectively. The mortality of rectal cancer cells was 98.1%, 76.2%, 37.8% at the ratio of efficacy to target of 30:1, 15:1, 1:1, respectively. CONCLUSION: The three-pronged approach may represent a powerful and safe means to selectively destroy cancer cells.

Combined Modality Therapy↗

PubMed2002

[Long-term results of extended parietal cell vagotomy in treatment of duodenal ulcers and their complications: report of 321 cases].

OBJECTIVE: To study the long-term results of extended parietal cell vagotomy (EPCV) in the treatment of patients with duodenal ulcer and their complications. METHODS: Form 1979 to 2001, EPCV was performed in 321 patients with duodenal ulcer and their complications. Of these patients 56 had chronic duodenal ulcer, 204 perforation, 16 hemorrhage and 40 stenosis. The following items were evaluated: complications of operation, gastric secretion, gastric emptying, endoscopical and radiographical findings, nutritional status, absorption function, and Visick scale. RESULTS: Postoperative follow-up ranged from 0.5 to 22.0 years (mean 11.3 years) in 289 of the 321 patients with a follow-up rate of 90.0%. Neither operative mortality nor dumping syndrome was noted. Episodic postprandial fullness occurred in 19 patients (6.5%), acid regurgitation in 17 (5.8%) and adhesive ileus in 4 (1.4%). Ulceration recurred in 16 patients (5.5%). Duodenal ulcer was seen in 8 patients (19.5%), hemorrhage in 0 (0%), stenosis in 2 (5.3%), and perforation in 6 (3.1%). Ulcers healed rapidly after medical therapy in 10 patients. Six patients received antrectomy and gastrectomy. In 289 (91.7%) patients of Grade I and II of Visick scale, 191 (95.3%) had perforation. CONCLUSIONS: EPCV is easy to perform with a low rate of post operative complication and ulcer recurrence. It should be a treatment of choice for acute perforation, hemorrhage or stenosis due to duodenal ulcer.

Duodenal Ulcer↗

PubMed2002

[Variations of cellular membrane phospholipids with genesis and hepatic metastasis of large intestine cancer].

OBJECTIVE: To separate and detect membrane phospholipids and study the relationship of metabolism and signal transduction pathways of membrane phospholipids with genesis and hepatic metastasis of large intestinal carcinoma. METHODS: Forty-eight cases of colorectal cancer were detected with high performance liquid chromatography. Membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestinal mucosa and hepatic metastasis of large intestine cancer were separated and analyzed. RESULTS: In primary foci, paratumor intestinal mucosa, and hepatic metastasis of the 48 cases, the contents (mg/g) of PI were: 0.92 +/- 0.12, 1.57 +/- 0.14, 1.54 +/- 0.15 respectively, and PC 56.47 +/- 5.33, 108.57 +/- 6.37, 116.35 +/- 6.85. The contents of PI and PC were higher in primary foci and hepatic metastasis than in paratumor mucosa (F = 363.10, 870.10, P < 0.01). The contents of PE in the three tissues were 18.23 +/- 3.56, 42.02 +/- 4.33, 79.51 +/- 5.52, and in hepatic metastasis was the highest (F = 1 149.63, P < 0.01). PI and PC in primary foci of hepatic metastatic group and nonmetastasis group were not significantly different (t = 3.55, P > 0.05). But the PE content was higher in hepatic metastasis than in primary foci (t = 115.87, P < 0.01). CONCLUSIONS: Membrane phospholipids have obvious variations in genesis and hepatic metastasis of large intestine cancer. Rises of PI and PC were associated with genesis of large intestine carcinoma. The increase of PE content is closely related to invasion and hepatic metastasis of large intestine cancer.

Adult↗

PubMed2002

[Enhancement of ionizing radiation on liposome-mediated gene delivery in human rectal cancer HR-8348 cells].

OBJECTIVES: To investigate the effect of ionizing radiation on liposome-mediated gene delivery and find out a way to improve gene transfection. METHODS: Prior to liposome transfection, HR-8348 cells were irradiated at doses of 0, 2, 4, 8 Gy selected according to the surviving fraction line of HR-8348 cells after different dosage of radiation. After 36 h of liposome transfection, green fluorocytes were counted. The transfection efficiency was figured out and compared with each other. RESULTS: The transfection efficiency of liposome-mediated gene delivery was 21.32%, 62.17%, 68.00%, 77.78% at the dose of 0, 2, 4, 8 Gy respectively and the clinical dose (2 Gy) was as high as 62.17%. Combined radiation and liposome-mediated gene delivery achieved the approximate transfection efficiency of virus vector. CONCLUSION: Ionizing radiation can improve the transfection efficiency of liposome-mediated gene delivery markedly and it is expected to treat human malignancy with liposome-mediated gene delivery combined with radiation.

Dose-Response Relationship, Radiation↗

PubMed2002

[Double promoters induct suicide gene target killing of 5-FU drug-fast cancer cells].

OBJECTIVE: To study target killing of 5-FU drug-fast cancer cells with thymidylate synthase (TS) and p16 gene promoters inducting TK gene expression. METHODS: TS promoter was inserted to 5' end and p16 promoter inserted to 3' end of TK cDNA sequence, constructing recombinant plasmid of pXJ41. Human rectal cancer cell lines of HR-8348 and normal peripheral blood mononuclear cells (PBMC) were transfected with the recombinant plasmid. Plating efficiency was counted and survival rates of cells were tested with MTT method. And suppression rates of xenograft tumors in nude mice were examined. RESULTS: Recombinant pXJ41 with double promotors and TK gene was transfected into HR-8348, and positive expression of TS and TK was observed. The expression of TK gene was consistent with TS expression. Plating efficiency was 9/300, 92/300 in transfected HR-8348 and contrast cells respectively (t = 33.885, P < 0.01). Cancer cell growth rate reduced markedly in the transfected group. The suppression rate of xenograft tumor growth was 74.5%. With the recombinant pXJ41 to transfect PBMC, p16 expression was positive, but TK and TS expressions were negative. No damnification was observed in PBMC. CONCLUSIONS: TS and p16 double promoters are capable of inducting TK target killing of 5-FU drug-fast cancer cells, thus protecting normal cells and improving safety of gene therapy.

Animals↗

PubMed2000

Cross-trait familial resemblance for resting blood pressure and body composition and fat distribution: The HERITAGE family study.

Cross-trait familial resemblance between resting blood pressure (BP) and body composition and fat distribution was examined in 98 Caucasian families participating in the HERITAGE Family Study by using a multivariate familial correlation model assessing both intraindividual and interindividual cross-trait correlations. The 520 family members were sedentary at baseline examination, and both resting systolic (SBP) and diastolic (DBP) BP were cross-analyzed with each of the following 10 indications of body composition and fat distribution: percent body fat (%BF), abdominal visceral fat (AVF), body mass index (BMI), fat-free mass (FFM), fat mass (FM), sum of eight skinfolds (SF), total abdominal fat (TAF), ratio of trunk-to-extremity skinfolds (TER), waist circumference (WAIST), ratio of waist-to-hip circumferences (WHR). Five of the variables were also corrected for fat mass (AVFf, TAFf, TERf, WAISTf, WHRf) to index these measures independent of total degree of adiposity. In general, the results suggested strictly intraindividual cross-trait resemblance, with occasional spouse cross-trait resemblance, but few or no sibling or parent-offspring cross-trait correlations. This pattern is largely consistent with nongenetic specific environmental determinants for the BP-body composition and fat distribution covariation, with possibly some common environmental influence between spouses and negligible genetic effects. The only findings suggesting any familial cross-trait resemblance were significant sibling correlations for DBP-FFM and DBP-WHR, although the parent-offspring correlation was not significant. These findings suggest that the observed BP-body composition and fat distribution cross-trait correlations in these sedentary families are probably not due to multifactorial effects such as polygenic and/or common familial environmental effects. Whether or not other factors such as nonadditive effects are involved warrants further investigation using other methods. Am. J. Hum. Biol. 12:32-41, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

PubMed2000

Major gene effect on subcutaneous fat distribution in a sedentary population and its response to exercise training: The HERITAGE Family Study.

Complex segregation analysis of baseline subcutaneous fat distribution and the change in response to exercise training (post-training minus baseline indices) was performed in a sample of 482 individuals from 99 Caucasian families who participated in the HERITAGE Family Study. The sum of skinfold (SF) thicknesses at eight sites, and the waist and hip circumferences were measured at baseline and after completing a 20-week exercise training program. The trunk-to-extremity ratio (TER) was calculated by dividing the sum of skinfold thicknesses at four trunk sites (subscapular + suprailiac + abdominal + midaxillary) by the sum of skinfold thicknesses at four extremity sites (triceps + biceps + medial calf + thigh). While SF was used to assess total subcutaneous adiposity, TER and the ratio of the waist-to-hip circumferences (WHR) were used to characterize subcutaneous fat distribution. Baseline TER and WHR were age-adjusted and age-SF-adjusted within four sex-by-generation groups. The changes of SF, TER, and WHR in response to training were adjusted for age effects alone and for the effects of age and baseline values. Baseline SF was influenced by a multifactorial component (30%) plus a major effect that may be environmental in origin accounting for 47% of the variance. Baseline TER was influenced by a multifactorial component (18%) and a major codominant gene (q(2) = 0.10), which accounted for 56% of the variance. The major gene effect was independent of total subcutaneous adiposity. Baseline WHR was regulated by a major codominant gene (q(2) = 0.15), which accounted for 48% of the variance. However, this major gene effect for baseline WHR should be interpreted with caution, given the estimates of the tau's under the general model. No familial effect was found for the changes in response to training for these subcutaneous adiposity and fat distribution phenotypes. Am. J. Hum. Biol. 12:600-609, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗