Familial resemblance of plasma apolipoprotein B: The Nancy study

Tiret, Laurence; Steinmetz, J.; Herbeth, Bernard; Visvikis, Sophie; Rakotovao, R; Ducimetière, Pierre; Cambien, François

doi:10.1002/gepi.1370070303

Cited by 16 publications

(10 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This estimated correla tion is comparable to that reported by others (0.13 to 0.47).23,24 Although examined in completely different study populations, most studies reported a codom inant m odel as the most parsim onious fit on their apoB data.20'22,24,25,31 A few studies, however, preferred a dom inant or recessive m odel. 19,23,26 The estimated rela tive frequency of the "lo w " apoB allele at 66% is in agreement with other reports.2 1 1 '22,24,25,31 These consis tent findings suggest that genetic control o f apoB levels is comparable in subjects with different dyslipidem ia phenotypes. Some o f the remaining differences in the results may be explained by the large differences in …”

Section: Discussionsupporting

confidence: 87%

Segregation Analysis of Plasma Apolipoprotein B Levels in Familial Combined Hyperlipidemia

Bredie

Drongelen

Kiemeney

et al. 1997

ATVB

View full text Add to dashboard Cite

Familial combined hyperlipidemia (FCH) is a heritable lipid disorder that is associated with an increased risk of premature cardiovascular disease. An elevated plasma apolipoprotein (apo) B concentration is reported to be a diagnostic feature of the disorder. Recently we demonstrated a strong relation between plasma apoB concentrations and the cholesterol concentration in VLDL plus LDL, both elevated in FCH families. Therefore, examination of the inheritance of elevated plasma apoB levels in FCH families may reveal important information about the mechanism responsible for the aggregation of elevated plasma lipids in FCH. This study included 663 Dutch family members in 40 families ascertained through FCH probands. Plasma apoB concentration correlated significantly with apoB-related cholesterol both in the probands and the relatives ( r =.83 and r =.90, respectively). Adjustment for age, sex, body mass index, and smoking habits accounted for 35.7% of the variation in apoB levels, and there was strong familial aggregation in adjusted apoB levels in these families. Complex segregation analysis was performed to determine the mechanism of inheritance behind this familial aggregation. The aggregation of elevated apoB levels was best explained by a major gene effect inherited by a codominant mechanism. Estimated mean apoB levels for the three supposed genotypes AA, AB, and BB were 111.5, 126.7, and 165.7 mg/dL, respectively, with relative frequencies of 43.5%, 44.9%, and 11.6%, respectively. In conclusion, despite assumed metabolic and genetic heterogeneity of FCH, there is clear evidence for a single gene effect on apoB concentrations in families ascertained through FCH. Linkage studies based on this analysis may further clarify the molecular basis of the apoB regulation in these families.

show abstract

Section: Discussionsupporting

confidence: 87%

Segregation Analysis of Plasma Apolipoprotein B Levels in Familial Combined Hyperlipidemia

Bredie

Drongelen

Kiemeney

et al. 1997

ATVB

View full text Add to dashboard Cite

show abstract

“…Again, in addition to potential factors discussed above, limited sample size might also be an explanation that prevented the second distribution component from being detectable in this study. For apo B-100, studies in a large Amish pedigree ascertained through a 13-year-old boy who died suddenly of advanced coronary atherosclerosis 24 and in a sample of 102 families volunteered for a free health checkup in the Preventive Center of Vandoeuvre-lès-Nancy of France 25 found no evidence of a major-gene effect, but a multifactorial component was significant. In contrast, 6 studies reported positive findings of a major gene influencing apo B-100 levels.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 In contrast to these positive findings, there also have been contradictory reports for apo A-1 9,18,23 and apo B-100. 24,25 Prospective epidemiological studies have provided evidence that apolipoprotein levels can be affected by physical activity and fitness levels. 26 In particular, apo A-1 levels have been reported to increase and apo B-100 levels to decrease 27,28 in response to exercise training.…”

mentioning

confidence: 99%

Segregation Analysis of Apolipoproteins A-1 and B-100 Measured Before and After an Exercise Training Program

Rice

Gagnon

et al. 2000

ATVB

Self Cite

View full text Add to dashboard Cite

Abstract-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 ⌬ (posttraining minus baseline) and was adjusted for age and the baseline (age-baselineadjusted 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. Key Words: commingling Ⅲ major gene effect Ⅲ major effect Ⅲ multifactorial effect

show abstract

“…The linkage disequilibrium coefficient (D 0 ) between the two PAI-1 polymorphisms was estimated by using loglinear model analysis [26]. PCOS women carrying the combination of the -844 A/A and non-5G/5G genotypes, or the coadunation of PAI-1 4G/4G and -844 non-G/G genotype, had significantly higher plasma PAI-1 levels than normal controls.…”

Section: Discussionmentioning

confidence: 99%

The plasminogen activator inhibitor-1 (PAI-1) gene −844 A/G and −675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome

Sun

Zhang

Liu

et al. 2009

Endocr

View full text Add to dashboard Cite

Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

show abstract

Familial resemblance of plasma apolipoprotein B: The Nancy study

Cited by 16 publications

References 32 publications

Segregation Analysis of Plasma Apolipoprotein B Levels in Familial Combined Hyperlipidemia

Segregation Analysis of Plasma Apolipoprotein B Levels in Familial Combined Hyperlipidemia

Segregation Analysis of Apolipoproteins A-1 and B-100 Measured Before and After an Exercise Training Program

The plasminogen activator inhibitor-1 (PAI-1) gene −844 A/G and −675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome

Contact Info

Product

Resources

About