Abstract

BackgroundThe -493G/T polymorphism in the microsomal triglyceride transfer protein (MTP) gene is associated with lower serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and longevity in several populations, but the results are inconsistent in different racial/ethnic groups. The current study was to investigate the plausible association of MTP -493G/T polymorphism with serum lipid levels and longevity in Zhuang long-lived families residing in Bama area, a famous home of longevity in Guangxi, China.MethodsThe MTP -493G/T was genotyped by PCR-restriction fragment length polymorphism in 391 Bama Zhuang long-lived families (BLF, n = 1467, age 56.60 ± 29.43 years) and four control groups recruited from Bama and out-of-Bama area with or without a familial history of exceptional longevity: Bama non-long-lived families (BNLF, n = 586, age 44.81 ± 26.83 years), Bama non-Zhuang long-lived families (BNZLF, n = 444, age 52.09 ± 31.91 years), Pingguo long-lived families (PLF, n = 658, age 50.83 ± 30.30 years), and Pingguo non-long-lived families (PNLF, n = 539, age 38.74 ± 24.69 years). Correlation analyses between genotypes and serum lipid levels and longevity were then performed.ResultsNo particularly favorable lipoprotein and clinical phenotypes were seen in BLF as compared to general families in the same area. Instead, the levels of total cholesterol (TC), TG, LDL-C, and the prevalence of dyslipidemia were significantly higher in the three Bama families as compared to the two non-Bama families (P < 0.01 for all). There were no differences in the allelic and genotypic frequencies among the tested cohorts (P > 0.05 for all), but the TT genotype tended to enrich in the three long-lived cohorts from both areas. In addition, the individuals harboring TT genotype exhibited lower LDL-C and TC levels in the overall populations and Bama populations with a region- and sex-specific pattern. Multiple linear regression analyses unraveled that LDL-C levels were correlated with genotypes in Bama combined population, BNLF, and the total population (P < 0.05 for each) but not in Pingguo populations; TC and HDL-C levels were correlated with genotypes in Bama combined population and BLF, respectively (P < 0.05 for each).ConclusionsMTP -493G/T polymorphism may play an important role in fashioning the serum lipid profiles of Bama populations, despite no direct association between MTP -493G/T and longevity was detected.

Highlights

  • A number of epidemiological studies have demonstrated that the elevation in plasma cholesterol is a key and independent risk factor in the etiology of coronary heart disease (CHD) which may further influence human mortality, aging, and lifespan [1,2,3]

  • Microsomal triglyceride transfer protein (MTP, or MTTP) is a heterodimeric lipid transfer protein mainly present in hepatocytes, enterocytes and myocytes which transfers lipid to a nascent apolipoprotein B molecule when it enters the lumen of the endoplasmic reticulum (ER), making it an indispensable genetic component in the maintenance of body cholesterol balance via pathways of absorption, synthesis, transfer, or secretion [2]

  • Most investigators reported an association between the microsomal triglyceride transfer protein (MTP) -493T allele and low levels of serum total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) [9,10,11,12,13], whereas others have either revealed an association of -493T allele with increased concentrations of TC, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apoB [14,15,16,17] or detected no relationship between this polymorphism and any lipid phenotype [18]

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Summary

Introduction

A number of epidemiological studies have demonstrated that the elevation in plasma cholesterol is a key and independent risk factor in the etiology of coronary heart disease (CHD) which may further influence human mortality, aging, and lifespan [1,2,3]. MTP gene has emerged as an appealing candidate gene involving in human longevity as its functions and essential position in lipoprotein assembly resemble apoE, the most extensively studied and consistently replicated gene affecting human longevity [5] In this context, there are reasons to assume that functional variants in the MTP gene may modulate MTP concentration or activity, affect plasma lipid levels and contribute to the development of atherosclerosis, CHD and aging, some of which have proved to be true [6,7]. The -493G/T polymorphism in the microsomal triglyceride transfer protein (MTP) gene is associated with lower serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and longevity in several populations, but the results are inconsistent in different racial/ethnic groups. The current study was to investigate the plausible association of MTP -493G/T polymorphism with serum lipid levels and longevity in Zhuang long-lived families residing in Bama area, a famous home of longevity in Guangxi, China

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