Article

The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study

The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University School of Medicine, Boston, MA, USA.
The Journal of Lipid Research (Impact Factor: 4.42). 12/2008; 50(3):565-73. DOI: 10.1194/jlr.P800041-JLR200
Source: PubMed

ABSTRACT

Low HDL-cholesterol (HDL-C) is associated with an increased risk for atherosclerosis, and concentrations are modulated by genetic factors and environmental factors such as smoking. Our objective was to assess whether the association of common single-nucleotide polymorphisms (SNPs) at ABCG5/G8 (i18429G>A, i7892T>C, Gln604GluC>G, 5U145A>C, Tyr54CysA>G, Asp19HisG>C, i14222A>G, and Thr400LysC>A) genes with HDL-C differs according to smoking habit. ABCG5/G8 SNPs were genotyped in 845 participants (243 men and 602 women). ABCG5/G8 (i7892T>C, 5U145A>C, Tyr54CysA>G, Thr400LysC>A) SNPs were significantly associated with HDL-C concentrations (P < 0.001-0.013) by which carriers of the minor alleles at the aforementioned polymorphisms and homozygotes for the Thr400 allele displayed lower HDL-C. A significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5/G8 (Gln604GluC>G, Asp19HisG>C, i14222A>G) SNPs displayed lower concentrations of HDL-C only if they were smokers (P = 0.001-0.025). Also, for ABCG8_Thr400LysC>A SNP, smokers, but not nonsmokers, homozygous for the Thr400 allele displayed lower HDL-C (P = 0.004). Further analyses supported a significant haplotype global effect on lowering HDL-C (P = 0.002) among smokers. In conclusion, ABCG5/G8 genetic variants modulate HDL-C concentrations, leading to an HDL-C-lowering effect and thereby a potential increased risk for atherosclerosis only in smokers.

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    • "Genetic epidemiological approaches may be useful for elucidating this inconsistency in the effects of habitual smoking on serum lipid profiles. In addition to our results, several joint effects of genetic factor and cigarette smoking on HDL cholesterol levels [7-10], LDL cholesterol levels [9] or triglyceride levels [11,12] have been already published. The polymorphism in PNPN11 gene, encoding Src homology 2 domain-containing protein tyrosine phosphatase-2, modulates the effect of cigarette smoking on serum HDL cholesterol levels and serum LDL cholesterol levels [9]. "
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    ABSTRACT: Several genetic polymorphisms have been reported to modify the effects of smoking on serum lipid levels. The objective of this study was to investigate whether longevity-associated mitochondrial DNA 5178 (Mt5178) C/A polymorphism modifies the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese subjects. A total of 394 male subjects (age, 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effect of Mt5178 C/A polymorphism and cigarette smoking on the risk of hypo-high-density lipoprotein (HDL) cholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia or hypertriglyceridemia was conducted. For subjects with Mt5178C, the risk of hypo-HDL cholesterolemia increased with the number of cigarettes smoked daily (P for trend = 0.001). On the other hand, the association between Mt5178A genotype and the risk of hypo-HDL cholesterolemia did not appear to depend on the number of cigarettes smoked daily. For those with Mt5178A, the risk of hyper-LDL cholesterolemia or hypertriglyceridemia increased with cigarettes smoked daily (P for trend = 0.017 and P for trend = 0.002, respectively). However, the association between Mt5178C genotype and the risk of hyper-LDL cholesterolemia or hypertriglyceridemia did not depend on the number of cigarettes smoked daily. The present results suggest that Mt5178 C/A polymorphism modulates the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.
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    • "In this way, Berge et al. established that the variation in plasma sterols levels is highly heritability and this polymorphism can partly explain this variation. In Puerto Rican population, the G allele summed to other variants in ABCG5 and G8 genes was significantly associated to lower concentrations of HDL-C in smokers, showing an interesting interaction between gene and smoking habit (Junyent et al., 2009). Moreover, Koeijvoets "

    Full-text · Article · Jun 2012 · International Journal of Morphology
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    ABSTRACT: Introducción: La Hipercolesterolemia Familiar (HF) es un desorden monogénico con una gran variabilidad interindividual en cuanto a expresión clínica, incluso en pacientes portadores de la misma mutación. Esto indica, que otros factores ambientales, genéticos o bien interacciones genes-ambiente, podrían jugar un importante papel. Hipótesis de trabajo: Los transportadores ABCG5/G8 ejercen un papel fundamental en el balance neto del metabolismo lipídico, principalmente sobre el c-HDL debido al papel que desempeñan dentro de la vía del transporte reverso del colesterol. La presencia de determinados polimorfismos en los genes ABCG5/G8 podría influir en el papel fisiológico de estos transportadores, modificando las concentraciones finales de lípidos plasmáticos. Objetivo principal: Analizar si la presencia del polimorfismo Y54C en el gen del transportador ABCG8 y otros SNPs seleccionados en los genes ABCG5/G8 (i7892A>G, i18429C>T, Gln604GluC>G, i11836G>A / 5U145T>G, Asp19HisG>C, i14222T>C, Thr400LysG>T), modulan las concentraciones de c-HDL en pacientes con HF heterocigota (HFh). Objetivos secundarios: Determinar el efecto de dichos polimorfismos sobre las concentraciones finales de colesterol total (CT), c-LDL, triglicéridos (TG), ApoA-I, ApoB y lipoproteína A, así como su influencia sobre marcadores plasmáticos de estrés oxidativo (lipoperóxidos y LDL oxidada). Estudiar interacciones entre estos SNPs y variables de riesgo en HFh (sexo, tabaco, obesidad, presencia de arco corneal y/o xantomas). Población, diseño y metodología: Los polimorfismos fueron genotipados en 586 pacientes con un diagnóstico genético de certeza de HF. Este diagnóstico se realizó mediante técnicas de ADN-microarray. Las determinaciones clínicas y bioquímicas fueron realizadas por un protocolo y procedimientos previamente establecidos. Resultados: Los individuos portadores del alelo A para el SNP i11836G>A y los individuos homocigotos GG para el SNP Y54C presentaron mayores concentraciones de c-HDL. A su vez, los sujetos portadores del SNP Gln604GluC>G y los homocigotos 6GG para Y54C, presentaron menores concentraciones de TG. Además, se observó una interacción entre algunos de los SNPs estudiados y el hábito tabáquico. De esta manera, ser fumador y portador del alelo minoritario para los SNPs i7892A>G, i18429C>T, i11836G>A en el gen ABCG5 y 5U145T>G en el gen ABCG8, está relacionado con menores concentraciones de c-HDL y mayores niveles de CT, TG y de c-VLDL, respectivamente. Además, ser portador del alelo minoritario T y G para los SNPs i18429C>T y Gln604GluC>G en el gen ABCG5 está relacionado con menores concentraciones de TG, solamente en sujetos no fumadores. Conclusiones: La presencia de determinados SNPs en los genes ABCG5/G8 modulan las concentraciones de lípidos plasmáticos en pacientes con HF. Este efecto a su vez, puede verse influenciado por la presencia del tabaco.
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