Vohl M C, Lamarche B, Bergeron J, Moorjani S, Prud'homme D, Nadeau A, Tremblay A, Lupien P J, Bouchard C, Després J P
CHUL Research Center and Laval University, Ste-Foy, Quebec, Canada.
Atherosclerosis. 1997 Feb 10;128(2):183-90. doi: 10.1016/s0021-9150(96)05985-0.
The aim of the present study was to examine the effect of variation at the apolipoprotein (apo) A-II gene locus on lipoprotein levels in visceral obesity. A total of 145 sedentary men, free from metabolic disorders requiring pharmacotherapy, were classified into two groups on the basis of their apo A-II-MspI genotype determined by the polymerase chain reaction: 1) 43 M1 carriers or M1M2, including two M1M1 homozygotes and 41 M1M2 heterozygotes, and 2) 102 M2M2 homozygotes for the presence of a MspI restriction site. The two genotypic groups did not differ for body mass index (BMI, expressed in kg/m2), body fat mass, visceral adipose tissue (AT) accumulation, as well as for insulin, glucose and free fatty acids levels measured in the fasting state and in response to an oral glucose tolerance test. In addition, 65 and 63% of M1 carriers had plasma HDL2 cholesterol levels and a HDL2/HDL3 cholesterol ratio below the 50th percentile of their distributions compared with 45%(P < 0.05) and 46%(P = 0.06), respectively, in M2M2 homozygotes. When subjects were further divided on the basis of visceral AT accumulation (below and above a value of 130 cm2), M1 carriers with low levels of visceral AT were characterized by high plasma HDL cholesterol and HDL2 cholesterol concentrations as well as by a higher HDL2/HDL3 ratio, compared with M1 carriers with high levels of visceral AT (> 130 cm2), or with M2M2 homozygotes with either a high or a low accumulation of visceral AT. Furthermore, M1 carriers with high levels of visceral AT showed a trend for lower plasma HDL2 cholesterol levels and were characterized by a significantly lower HDL2/HDL3 cholesterol ratio compared with the other three groups. No difference in HDL and HDL2 cholesterol levels and in the HDL2/HDL3 cholesterol ratio was noted when M2 homozygotes with lower versus higher levels of visceral AT were compared. The contribution of hyperinsulinemia was also examined by dividing subjects on the basis of the 50th percentile of the integrated insulin response to an oral glucose challenge. Significantly lower plasma HDL2 cholesterol levels and a reduced HDL2/HDL3 cholesterol ratio were noted among M1 carriers with high plasma insulin responses compared with M1 carriers with low insulin responses. Among M2M2 homozygotes, no difference was noted in plasma HDL cholesterol and in HDL2 cholesterol concentrations between men with low versus high insulin responses to the oral glucose load. These results suggest that the apo A-II-MspI polymorphism could modulate plasma HDL cholesterol levels among visceral obese, insulin-resistant men.
本研究的目的是检测载脂蛋白（apo）A-II基因位点变异对内脏型肥胖患者脂蛋白水平的影响。共有145名久坐不动且无需要药物治疗的代谢紊乱的男性，根据聚合酶链反应确定的apo A-II-MspI基因型分为两组：1）43名M1携带者或M1M2，包括2名M1M1纯合子和41名M1M2杂合子；2）102名存在MspI限制性位点的M2M2纯合子。两组在体重指数（BMI，单位为kg/m2）、体脂肪量、内脏脂肪组织（AT）堆积以及空腹状态下和口服葡萄糖耐量试验后的胰岛素、葡萄糖和游离脂肪酸水平方面无差异。此外，65%和63%的M1携带者血浆HDL2胆固醇水平和HDL2/HDL3胆固醇比值低于其分布的第50百分位数，而M2M2纯合子中这一比例分别为45%（P<0.05）和46%（P = 0.06）。当根据内脏AT堆积情况（低于和高于130 cm2）进一步划分受试者时，与内脏AT水平高（>130 cm2）的M1携带者或内脏AT堆积高低不同的M2M2纯合子相比，内脏AT水平低的M1携带者具有高血浆HDL胆固醇和HDL2胆固醇浓度以及更高的HDL2/HDL3比值的特征。此外，与其他三组相比，内脏AT水平高的M1携带者血浆HDL2胆固醇水平有降低趋势，其特征是HDL2/HDL3胆固醇比值显著降低。比较内脏AT水平低与高的M2纯合子时，HDL和HDL2胆固醇水平以及HDL2/HDL3胆固醇比值无差异。还通过根据口服葡萄糖激发试验的胰岛素综合反应的第50百分位数对受试者进行划分来研究高胰岛素血症的作用。与胰岛素反应低的M1携带者相比，胰岛素反应高的M1携带者血浆HDL2胆固醇水平显著降低，HDL2/HDL3胆固醇比值降低。在M2M2纯合子中，口服葡萄糖负荷后胰岛素反应低与高的男性之间，血浆HDL胆固醇和HDL2胆固醇浓度无差异。这些结果表明，apo A-II-MspI多态性可能在内脏型肥胖、胰岛素抵抗的男性中调节血浆HDL胆固醇水平。
