No common major gene for apolipoprotein A-I and HDL3-C levels: Evidence from bivariate segregation analysis

BackgroundTriglyceride/HDL cholesterol ratio (TG/HDL-C) is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C.ResultsTwo populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs) and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs) were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0). Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002), but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p < 0.001). Commingling analyses showed that more than one-component distribution models were the best-fit models to explain the variance in both populations. Complex segregation analysis by regressive models revealed that in both samples the best-fit model of TG/HDL-C was the model of environmental effects plus familial correlation, in which significant parent-offspring and sibling correlations were demonstrated. Models of major gene effects were rejected in both samples.ConclusionVariations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families.

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“…The results were compatible with previous high risk population studies [18,19]. The reason is following.…”

Section: Discussionsupporting

confidence: 92%

Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

Chien

Hsu

et al. 2003

BMC Genet

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“…Moreover, in other studies, a major-locus hypothesis was not conclusive, unless it was paired with HDL-C 10 or a second major locus was involved. 22 Recently, Livshits et al 15 found a major locus influencing plasma apo A-1 levels also influencing plasma HDL 3 -C concentrations in a random sample of 228 Israeli pedigrees; however, Juo et al 16 used 137 selected families ascertained through probands undergoing elective diagnostic coronary angiography at the Johns Hopkins Hospital and reported no common major locus for these phenotypes. In addition, 2 recent studies used the GAW8 Berkeley data set, 21 and the 137 selected families from the Johns Hopkins Hospital 22 have provided evidence of 2 major loci affecting apo A-1 levels.…”

Section: Discussionmentioning

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

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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

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“…Individual polymorphisms of apolipoprotein gene cluster, APOA1/C3/A4/A5 [3,[8][9][10][11][12] are located on chromosome 11 and N10 single nucleotide polymorphisms were found in this gene cluster [13]. Previous case-control association studies showed that APOA1 −75GNA polymorphism over the promoter site, was associated with HDL level [14,15].…”

Section: Introductionmentioning

confidence: 99%

Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population

Chien

Chen

Hsu

et al. 2008

Clinica Chimica Acta

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No common major gene for apolipoprotein A-I and HDL3-C levels: Evidence from bivariate segregation analysis

Cited by 7 publications

References 32 publications

Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

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

Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population

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