Biomedical subjects

C Bouchard

Publications and source records attributed to C Bouchard.

At least 163 records · Page 9Linked to original sources

PubMed2000

Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study.

The gene-gene interactions between markers in the alpha2-, beta2-, and beta3-adrenergic receptor (ADR) genes and obesity-related phenotypes were studied in the Quebec Family Study (QFS) cohort. The prevalence of the Arg allele of the Arg16Gly polymorphism in the beta2-ADR gene was higher (49%) in males with a body mass index (BMI) of 35 kg/m2 or higher versus those with a BMI less than 35 kg/m2 (33%; P = .010). The beta2-ADR gene Arg16Gly and Gln27Glu polymorphisms were associated with plasma total and low-density lipoprotein (LDL) cholesterol concentrations. In addition, the homozygotes for the 6.3-kb allele of DraI polymorphism in the alpha2-ADR gene had the lowest mean abdominal subcutaneous fat area (P = .012) and total fat area (P = .003), as well as insulin area, under the curve during an oral glucose tolerance test ([OGTT] P = .004). Several ADR gene-gene interaction effects on abdominal fat distribution and plasma lipids were detected. First, significant interactions between alpha2- and beta3-ADR genes were observed on total (P = .015) and subcutaneous (P = .004) abdominal fat. Second, interaction effects between alpha2- and beta2-ADR gene variants influenced total, high-density lipoprotein (HDL), and LDL cholesterol concentrations. Finally, there were interactions between markers within the beta2-ADR gene affecting plasma triglyceride concentrations and subcutaneous abdominal fat. From these results, we conclude that polymorphisms in the ADR genes contribute to body fat and plasma lipid variability in men. Gene-gene interactions among the ADR genes contribute to the phenotypic variability in abdominal obesity and plasma lipid and lipoprotein, but not in visceral fat levels.

Abdomen↗

PubMed2000

A polymorphism of the 5'-flanking region of the glucocorticoid receptor gene locus is associated with basal cortisol secretion in men.

There is growing evidence that cortisol secretion and/or metabolism is associated with cardiovascular risk factors. Previous studies have shown that cardiovascular risk factors are associated with stimulated cortisol secretion and not with basal cortisol secretion. With the restriction enzyme Tth111I, a variant of the 5'-flanking region of the glucocorticoid receptor gene locus (GRL) was identified. The genotypes were compared for measurements of cortisol secretion and cardiovascular risk factors in a cohort (N = 284) of randomly selected middle-aged men. The frequency of the 3.4/3.4-, 3.4/3.8-, and 3.8/3.8-kilobase (kb) genotypes was 49.6%, 41.4%, and 9.0% respectively. The 3.8-kb homozygotes showed higher total and evening cortisol levels with a trend for elevated levels over the day. Neither stimulated or suppressed cortisol secretion nor anthropometric, endocrine, metabolic, and hemodynamic cardiovascular risk factors were significantly different among the genotypes. Since the polymorphism studied herein is localized at the 5'-flanking region of the GRL, the results suggest that elevated basal cortisol secretion is associated with a polymorphism of the promoter region.

Alleles↗

PubMed2000

A genetic study of sex hormone--binding globulin measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and a major gene effect were assessed for baseline serum sex hormone-binding globulin (SHBG) levels and the response (post-training minus baseline) to a 20-week endurance training program in a selected sample of 428 non-obese nonhypertensive individuals from 99 white families who were sedentary at baseline in the HERITAGE Family Study. Baseline SHBG levels were not normally distributed, and were therefore logarithmically transformed prior to genetic analyses. In a sample without postmenopausal mothers, maximal (genetic and familial environmental) heritabilities were 50% averaged across sexes, 73% in men, 50% in women, and 31% in men versus women for the age-body mass index (BMI)-adjusted baseline. The estimate reached 64% when the baseline was further adjusted for the effects of estradiol, fasting insulin, and testosterone levels. For the response to training, no sex difference was found and the heritability reached about 25% to 32%. Segregation analysis was separately performed in the whole sample and in the sample without postmenopausal mothers. In addition to a multifactorial effect for both the baseline and the response to training, a major effect for the baseline appeared to be familial environmental in origin, whereas a major effect for the response to training was Mendelian in nature. The major gene effect for the response to training in the whole sample was undetectable in the sample without postmenopausal mothers, and it is therefore possible that the postmenopausal mothers, characterized by decreased sex hormones with or without estrogen replacement therapy for menopause, produced some confounding effects. In addition, the reduced sample size might also be a plausible candidate explanation. The novel finding in this study is that baseline SHBG levels and the response to training were influenced by a multifactorial effect with sex difference for the baseline. The response to training appeared to be additionally influenced by a single recessive locus that is independent of baseline SHBG levels.

Adult↗

PubMed2000

Familial aggregation of stroke volume and cardiac output during submaximal exercise: the HERITAGE Family Study.

Familial aggregation of stroke volume (SV) and cardiac output (Qc by CO2 rebreathing) at 50 Watts (W) and 60 % of maximal oxygen uptake (VO2max) as well as their changes in response to a 20-week endurance exercise training program was assessed in 99 Caucasian families who participated in the HERITAGE Family Study. In order to interpret familial influences independent of effects of age, sex, and body size (indexed by body surface area here), SV and Qc levels were adjusted for these primary parameters prior to genetic analysis within four sex-by-generation groups (the responses to training were additionally adjusted for their baseline values). Maximal heritabilities for baseline SV, Qc, and their changes in response to training during the two stages of submaximal exercise were estimated using a familial correlation model. At 50W, maximal heritabilities reached 41% and 42% for baseline SV and Qc, respectively, and were 29% and 38% for the respective responses to training. At 60% of VO2max, maximal heritabilities reached 46 % for baseline SV and Qc, and were 24% and 30% for the respective responses to training. Generally there were no meaningful differences between the maximal heritabilities at 50 W and 60% of VO2max. However, the maximal heritabilities for the baseline were slightly higher than the estimates for the changes in response to training. Based upon results arising from these non-obese, non-hypertensive, and sedentary families, we found that SV and Qc at 50 W and 60% of VO2max as well as their changes in response to the 20-week endurance exercise training were moderately heritable. Not only genetic determinants but also familial non-genetic factors might attribute to the observed patterns of familial aggregation of SV and Qc during submaximal exercise in the present study.

Adult↗

PubMed2000

Widely meshed autograft associated with cultured autologous epithelium for the treatment of major burns in children: report of 12 cases.

This is a retrospective study of the combination of widely meshed autograft and autologous cultured keratinocytes. We used this method faced with the lack of allogenic skin, as an alternate to the Cuono method. Twelve children suffering extensive burn injury (deep burns of 60%+/-16 of the total body surface) underwent this grafting procedure. The surgical treatment consisted of an early surgical excision, with an immediate coverage by autografts as much as possible. When cultured epithelium was available, a large mesh autograft was applied and covered with cultured epidermis sheets during the same operative procedure. The rate of take was of 84% (+/- 12). No secondary graft loss was observed. This means of coverage appeared reliable and resistant. On average, this method allowed the epidermization of 30% (+/-9) of the total body surface of the children. The average hospital stay of the children was 64+/-20 days. All the children recovered to lead a normal life. The school delay after rehabilitation is one year. This technique is an alternative to Cuono's method when allografts are missing. The combination of autograft and autologous cultured epidermis sheets appeared more effective than one of these techniques applied alone, as if the suggested coupling induced a synergy.

Adolescent↗

PubMed2000

Gene-diet interactions in obesity.

A considerable amount of research on the genetics of obesity has been reported in the past few years. Despite evidence that genetic factors play a significant role in the etiology of this nutritional disease and the increasing number of obesity genes identified, relatively little is known about the role of genes in the response of obesity phenotypes to alterations in energy balance or diet composition. This is especially true for dietary fat, which is known to be associated with obesity at the population level. The aim of this review was to summarize the evidence currently available about the role of gene-nutrient interactions in human obesity. Evidence from both genetic epidemiology and molecular epidemiology studies suggests that genetic factors are involved in determining the susceptibility to gaining or losing fat in response to diet or the risk of developing some of the comorbidities generally observed in obese individuals. Recent evidence suggests that quantitative trait loci identified from animal models of diet-induced obesity could influence body fat in humans. Despite the limited number of studies, the evidence on gene-diet interactions in obesity is convincing. More research is needed to identify the genes responsible for these interaction effects, and the use of animal models of diet-induced obesity represents a promising approach. Finally, data on children are needed to allow assessment of the tracking of nutrient intake between childhood and adulthood. In addition, gene-diet interactions in children need to be investigated to determine whether the genes involved are the same as those found in adults.

Animals↗

PubMed2000

Adaptation to a standardized training program and changes in fitness in a large, heterogeneous population: the HERITAGE Family Study.

PURPOSE: This paper describes the variations in response to a standardized, computer-controlled training program. METHODS: Steady-state heart rate (HR) and oxygen intake (VO2) of 614 healthy, sedentary men and women aged 16-65 yr were measured during three cycle ergometer exercise tests. The HR associated with 55, 65, 70, and 75% of each subject's pretraining VO2max was used to prescribe exercise intensity. Subjects exercised three times a week, beginning at a HR associated with 55% VO2max for 30 min. Duration and intensity was gradually increased over 20 wk of training. The duration and HR of each training session were controlled by a computer. RESULTS: Using the linear relationship between HR, VO2 and power output (PO), PO were predicted for each of 60 training sessions at the respective programmed HR. The average ratio of the actual training HR to programmed HR was 0.99. It was hypothesized that participants whose actual training PO exceeded their predicted PO would improve VO2max more than those whose actual PO was less than their predicted PO. Using the ratio of actual/predicted PO determined after the training was over, participants were arbitrarily assigned to three groups: 128 participants had low (LO) ratios (0.65-0.84), 408 had average (AV) ratios (0.85-1.14), and 78 had high (HI) ratios (1.15-1.34). Secondary analysis showed that the training program significantly increased mean VO2max of all three groups. Those who had a smaller increase in training PO (LO) had significantly less increase in VO2max than those with larger increases in PO (HI). CONCLUSION: People who exercise at a HR associated with the same %VO2max can vary substantially in their training PO, in their rate of increase in PO over a 20-wk training program, and in improvement of their VO2max.

Adaptation, Physiological↗

PubMed2000

The association between vigorous physical activities and fat deposition in male adolescents.

PURPOSE: The aim of this study was to investigate the association between participation in vigorous physical activities (VPA) and indicators of adiposity and fat distribution in male adolescents. METHODS: Subjects were classified on the basis of the number of reported 15-min periods over 3 d during which VPA were performed. RESULTS: Body weight, fat mass, body mass index, sum of six subcutaneous skinfolds, trunk and extremity skinfolds, and trunk to extremity skinfolds ratio (T/E ratio) were all significantly and inversely related to a higher VPA participation. Moreover, T/E ratio was significantly lower in the subgroup reporting a mean of 7.8 15-min periods of activity for 3 d (equivalent to a mean of 39 min x d(-1)) compared with subjects reporting no participation. This decrease in T/E ratio was more pronounced in subjects reporting a mean of 13.6 15-min periods of VPA for 3 d. CONCLUSION: These observations reinforce the idea that excess abdominal fat accumulation can be prevented by regular participation in vigorous physical activities.

Abdomen↗

PubMed2000

Familial risk ratios for high and low physical fitness levels in the Canadian population.

PURPOSE: To estimate the familial risk of being physically fit or unfit in Canada. METHODS: The sample consisted of 11,680 participants from 4144 nuclear families of the 1981 Canada Fitness Survey. Indicators of physical fitness included estimated physical working capacity at a heart rate of 150 beats x min(-1) derived from a step test (PWC150), hand grip strength, sit-ups, and trunk flexibility. Probands were defined as reference individuals who were physically fit (95th, 85th, and 75th percentiles) or physically unfit (25th, 15th, and 5th percentiles) for each fitness indicator, respectively. RESULTS: Standardized risk ratios, adjusted for age and sex (SRR), for spouses and first-degree relatives of probands exceeding the 95th percentile are 1.63 and 1.81 for PWC150, 2.38 and 3.16 for grip strength, 2.63 and 3.98 for sit-ups, and 2.59 and 3.56 for trunk flexibility, respectively, whereas the SRR for spouses and first-degree relatives of probands below the 5th percentile are 1.54 and 1.34 for PWC150, 1.83 and 1.85 for grip strength, 1.13 and 1.53 for sit-ups, and 1.42 and 1.84 for trunk flexibility, respectively. The familial risks tend to be greatest at the extremes (95th and 5th percentiles) and the risks for first-degree relatives of physically fit probands are generally greater than those for spouses for grip strength, sit-ups and trunk flexibility, whereas those for PWC150 show no clear pattern. CONCLUSION: There is significant familial risk for being physically fit or unfit in the Canadian population. The pattern of SRR suggests that the familial risk for indicators of strength and flexibility may be due, in part, to genetic factors, whereas the shared family environment is largely contributing to the familial risk for PWC150.

Adolescent↗

PubMed2000

Familiality of triglyceride and LPL response to exercise training: the HERITAGE study.

PURPOSE: The main purpose of the present investigation was to test whether and to what extent familial/genetic factors are involved in the changes of postheparin lipoprotein lipase (deltaPH-LPL) activity and triglyceride (deltaTG) levels in response to exercise training. Additional hypotheses were also tested as to whether there were familial/genetic factors shared by baseline and the corresponding response to exercise training (i.e., by baseline triglyceride (TG(B)) and deltaTG and by baseline postheparin lipoprotein lipase (PH-LPL(B)) and deltaPH-LPL activity). METHODS: Serum TG and PH-LPL were measured in 459 subjects from 99 sedentary Caucasian families of the HERITAGE Family study before (baseline) and after completing a 20 wk (3 times per week) exercise training protocol. The training protocol had a target intensity of 75% of the heart rate associated with baseline VO2max during the last 6 wk. PH-LPL activity was measured in the study subjects. Both univariate and bivariate familial correlation analyses were applied to the baseline and response data. RESULTS: The maximal heritabilities for deltaTG and deltaPH-LPL activity were 22% and 15%, respectively. There were no common familial factors for TG(B) and deltaTG, nor were there any for PH-LPL(B) and deltaPH-LPL. However, we found that there were common familial factors underlying deltaTG and deltaPH-LPL; these familial factors seemed to differ across sex and generation groups. CONCLUSION: Although there were no common familial factors underlying the covariation between the baseline triglyceride and PH-LPL activity and the corresponding responses to exercise training (i.e., TG(B) with deltaTG or PH-LPL(B) with deltaPH-LPL), the deltaTG and deltaPH-LPL covariation apparently share some common familial determinants.

Adolescent↗

PubMed2000

A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status.

PURPOSE: In a case control study, we examined the allelic frequencies and genotype distributions of two restricted fragment length polymorphisms (RFLP) in the alpha-2A-adrenoceptor gene (ADRA2A) and beta-2-adrenoceptor gene (ADRB2) among elite endurance athletes (EEA) and sedentary controls (SC). METHODS: The EEA group included 148 Caucasian male subjects recruited on the basis that they had a VO2max > 74 mL O2 x kg(-1) x min(-1). The SC group comprised 149 unrelated sedentary male subjects, all Caucasians, from the Quebec Family Study. After digestion with the restriction enzymes Dra I (ADRA2A) and Ban I (ADRB2), Southern blotting and hybridization techniques were used to detect the mutations in the two ADR genes, which are encoded on chromosomes 10 (q24-26) and 5 (q31-32), respectively. RESULTS: For the Dra I ADRA2A RFLP, we observed a significant difference in genotype distributions between the two groups (P = 0.037). A higher frequency of the 6.7-kb allele was observed in the EEA group compared with the SC group (P = 0.013). No statistically significant difference was found between groups for the Ban I ADRB2 polymorphic site. Genotype frequencies for both genes in both groups were in Hardy-Weinberg equilibrium. CONCLUSIONS: In summary, we found evidence that ADRA2A gene variability detected with Dra I is weakly associated with elite endurance athlete status, and we conclude that genetic variation in the ADRA2A gene or a locus in close proximity may play a role in being able to sustain the endurance training regimen necessary to attain a high level of maximal aerobic power.

Alleles↗

PubMed2000

AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study.

We investigated the association between angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphisms and exercise training responses of resting and exercise blood pressure (BP). BP at rest and during submaximal (50 watts) and maximal exercise tests was measured before and after 20 wk of endurance training in 476 sedentary normotensive Caucasian subjects from 99 families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR-based methods. Men carrying the AGT MM and MT genotypes showed 3. 7 +/- 0.6 and 3.2 +/- 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts (DBP(50)), whereas, in the TT homozygotes, the decrease was 0.4 +/- 1.0 mmHg (P = 0.016 for trend, adjusted for age, body mass index, and baseline DBP(50)). Men with the ACE DD genotype showed a slightly greater decrease in DBP(50) (4.4 +/- 0.6 mmHg) than the II and ID genotypes (2.8 +/- 0.7 and 2.4 +/- 0.5 mmHg, respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction effect between the AGT and ACE genes was noted for DBP(50); the AGT TT homozygotes carrying the ACE D allele showed no response to training. Men with the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute maximal exercise at baseline. However, the difference disappeared after the training period. No associations were found in women. These data suggest that, in men, the genetic variation in the AGT locus modifies the responsiveness of submaximal exercise DBP to endurance training, and interactions between the AGT and ACE loci can alter this response.

Adult↗

PubMed2000

The Na(+)-K(+)-ATPase alpha2 gene and trainability of cardiorespiratory endurance: the HERITAGE family study.

The Na(+)-K(+)-ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance performance. This study aimed to investigate the associations between genetic variants at the Na(+)-K(+)-ATPase alpha2 locus and the response (Delta) of maximal oxygen consumption (VO(2 max)) and maximal power output (W(max)) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. VO(2 max) and W(max) were measured during two maximal cycle ergometer exercise tests before and again after the training program, and restriction fragment length polymorphisms at the Na(+)-K(+)-ATPase alpha2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the alpha2 haplotype and DeltaVO(2 max) (P = 0.054) and stronger linkages between the alpha2 exon 21-22 marker (P = 0.005) and alpha2 haplotype (P = 0.003) and DeltaW(max). In the whole cohort, DeltaVO(2 max) in the 3.3-kb homozygotes of the exon 1 marker (n = 5) was 41% lower than in the 8.0/3.3-kb heterozygotes (n = 87) and 48% lower than in the 8.0-kb homozygotes (n = 380; P = 0.018, adjusted for age, gender, baseline VO(2 max), and body weight). Among offspring, 10.5/10.5-kb homozygotes (n = 14) of the exon 21-22 marker showed a 571 +/- 56 (SE) ml O(2)/min increase in VO(2 max), whereas the increases in the 10.5/4.3-kb (n = 93) and 4.3/4.3-kb (n = 187) genotypes were 442 +/- 22 and 410 +/- 15 ml O(2)/min, respectively (P = 0.017). These data suggest that genetic variation at the Na(+)-K(+)-ATPase alpha2 locus influences the trainability of VO(2 max) in sedentary Caucasian subjects.

Adaptation, Physiological↗

PubMed2000

Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study.

This study aimed to identify human genomic regions that are linked to maximal oxygen uptake (VO(2 max)) in sedentary individuals or to the responsiveness of VO(2 max) to a standardized endurance training program. The results of a genomic scan based on 289 polymorphic markers covering all 22 pairs of autosomes performed on the Caucasian families of the HERITAGE Family Study are presented. The mean spacing of the markers was 11 cM, and a total of 99 families and 415 pairs of siblings were available for the study. VO(2 max) in the sedentary state was adjusted for the effects of age, sex, body mass, fat mass, and fat-free mass, whereas the VO(2 max) response was adjusted for age and baseline level of the phenotype. Two analytic strategies were used: a single-point linkage procedure using all available pairs of siblings (SIBPAL) and a multipoint variance components approach using all the family data (SEGPATH). Results indicate that linkages at P values of 0.01 and better are observed with markers on 4q, 8q, 11p, and 14q for VO(2 max) before training and with markers on 1p, 2p, 4q, 6p, and 11p for the change in VO(2 max) in response to a 20-wk standardized endurance training program. These chromosomal regions harbor many genes that may qualify as candidate genes for these quantitative traits. They should be investigated in this and other cohorts.

Adolescent↗

PubMed2000

Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study.

It has been suggested that genetic variation in the angiotensin-converting enzyme (ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian (n = 476) and black (n = 248) subjects. Phenotypes measured were oxygen uptake (VO(2)), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximal VO(2) (VO(2 max))] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60% VO(2 max)). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant (P values from 0.042 to 0. 0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14-38% greater increase with training in VO(2 max), VO(2) at 80% of VO(2 max), and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.

Adult↗

PubMed2000

No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status.

Several studies have reported that the insertion (I) allele of the angiotensin-converting enzyme (ACE) I/deletion (D) polymorphism is associated with enhanced responsiveness to endurance training and is more common in endurance athletes than in sedentary controls. We tested the latter hypothesis in a cohort of 192 male endurance athletes with maximal oxygen uptake >/=75 ml. kg(-1). min(-1) and 189 sedentary male controls. The ACE ID polymorphism in intron 16 was typed with the three-primer polymerase chain reaction method. Both the genotype (P = 0.214) and allele (P = 0.095) frequencies were similar in the athletes and the controls. Further analyses in the athletes revealed no excess of the I allele among the athletes within the highest quartile (> 80 ml. kg(-1). min(-1)) or decile (>83 ml. kg(-1). min(-1)) of maximal oxygen uptake. These data from the GENATHLETE cohort do not support the hypothesis that the ACE ID polymorphism is associated with a higher cardiorespiratory endurance performance level.

Alleles↗

PubMed2000

Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis.

The functional 5A/6A polymorphism of the stromelysin-1 promoter has been implicated as a potential genetic marker for the progression of angiographically determined atherosclerosis in patients with coronary artery disease. Recently, a novel interleukin-6 (IL-6) gene functional G/C polymorphism at -174 in the promoter has also been reported. In this study, we analyzed the relation of these two polymorphisms with carotid artery atherosclerosis in 109 randomly selected, middle-aged men without exercise-induced ischemia. Atherosclerosis was quantified as intima-media thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (P:=0.015) associated with IMT, and this relation remained (P:=0.033) after adjustments for age, cardiorespiratory fitness, body mass index, smoking, LDL cholesterol, and systolic blood pressure and for sonographers. The 5A/6A polymorphism independently explained 7% of the variance in carotid bifurcation IMT. The IL-6 polymorphism was also significantly associated (P:=0. 036) with increased IMT, with men homozygous for the G allele having IMT that was 11% greater than men homozygous for the C allele. Men who were homozygous for both the 6A and G alleles had an covariate adjusted IMT that was 36% greater than men who were homozygous for neither allele (P:<0.003). These data suggest that genetic factors that predispose to reduced matrix remodeling (stromelysin 6A allele) and to increased inflammation (IL-6 G allele) combine to increase susceptibility for intima-media thickening in the carotid bifurcation, a predilection site for atherosclerosis.

Carotid Stenosis↗

PubMed2000

Segregation analysis of apolipoproteins A-1 and B-100 measured before and after an exercise training program: the HERITAGE Family Study.

Complex segregation analyses of apolipoproteins (apo) A-1 and B-100 were performed in a sample of 520 individuals from 99 white families who participated in the HERITAGE Family Study. In these sedentary families, plasma apo A-1 and B-100 concentrations were measured before and after a 20-week endurance exercise training program. Baseline apo A-1 and B-100 were adjusted for the effects of age (age-adjusted baseline apo A-1 and B-100) and for the effects of age and BMI (age-BMI-adjusted baseline apo A-1 and B-100). The change in response to training was computed as a simple Delta (posttraining minus baseline) and was adjusted for age and the baseline (age-baseline-adjusted apo A-1 and B-100 responses to training). In the present study, a major gene could not be inferred for baseline apo A-1. Rather, we found a major effect along with a multifactorial effect accounting for 8% to 9% and 51% to 56% of the variance, respectively. In addition, no clear evidence supported a major-gene effect for its response to training, whereas the transmission of a major effect from parents to offspring was ambiguous, ie, genetic in nature or familial environmental in origin. The major effect accounted for 15% of the variance, with an additional 21% and 58% of the variance being accounted for by a multifactorial effect in parents and offspring, respectively. It is interesting to have obtained evidence of a putative recessive major locus for baseline apo B-100, which accounted for 50% to 56% of the variance, with an additional 25% to 29% of the variance due to a multifactorial effect. In contrast, no major effect for its response to training was identified, although a multifactorial effect was found that accounted for 27% of the variance. The novel findings arising from the present study are summarized as follows. Baseline apo A-1 and its response to training were influenced by a major effect and a multifactorial effect. Baseline apo B-100 was influenced by a putative major recessive gene with a multifactorial component, but its response to training was influenced solely by a multifactorial component in these sedentary families.

Adolescent↗