Acton S, Osgood D, Donoghue M, Corella D, Pocovi M, Cenarro A, Mozas P, Keilty J, Squazzo S, Woolf E A, Ordovas J M
Millennium Pharmaceuticals, Inc, Cambridge, MA, USA.
Arterioscler Thromb Vasc Biol. 1999 Jul;19(7):1734-43. doi: 10.1161/01.atv.19.7.1734.
The scavenger receptor class B type I (SR-BI) is a lipoprotein receptor that has been shown to be important in high density lipoprotein cholesterol (HDL-C) metabolism in mice. To determine its role in humans, we have characterized the human SR-BI gene and investigated its genetic variation in 489 white men and women. Five variants were demonstrated: 2 in introns (3 and 5) and 3 in exons (1, 8, and 11). Three variants at exons 1 and 8 and intron 5 with allele frequencies >0.1 were used to examine associations with lipid or anthropometric variables. The exon 1 variant was significantly (P<0.05) associated with increased HDL-C and lower low density lipoprotein cholesterol (LDL-C) values in men, but no associations were observed in women. The exon 8 variant was associated in women with lower LDL-C concentrations (3.05+/-0.98 mmol/L and 3.00+/-0.93 mmol/L for heterozygotes and homozygotes, respectively) compared with women homozygous for the common allele (3.39+/-1.09 mmol/L, P=0. 043). No associations for this variant were observed in men. Women carriers of the intron 5 variant showed a higher body mass index (23. 8+/-3.8 kg/m2, P=0.031) than those women homozygous for the common allele (22.4+/-3.4 kg/m2). Similar results were observed after haplotype analysis. Multiple regression analysis using HDL-C, LDL-C, and body mass index as dependent variables and age, sex, and each of the genetic variants as predictors also provided similar results. The associations found with both LDL-C and HDL-C suggest that SR-BI may play a role in the metabolism of both lipoprotein classes in humans.
I型B类清道夫受体（SR-BI）是一种脂蛋白受体，已证明其在小鼠高密度脂蛋白胆固醇（HDL-C）代谢中起重要作用。为确定其在人类中的作用，我们对人类SR-BI基因进行了特征分析，并研究了489名白人男性和女性的基因变异情况。共发现5个变异：2个在内含子（3号和5号），3个在外显子（1号、8号和11号）。使用外显子1号、8号和内含子5号中3个等位基因频率>0.1的变异来研究与血脂或人体测量变量的关联。外显子1号变异在男性中与HDL-C升高和低密度脂蛋白胆固醇（LDL-C）值降低显著相关（P<0.05），但在女性中未观察到关联。外显子8号变异在女性中与LDL-C浓度降低相关（杂合子和纯合子的LDL-C浓度分别为3.05±0.98 mmol/L和3.00±0.93 mmol/L），而常见等位基因纯合子女性的LDL-C浓度为3.39±1.09 mmol/L（P=0.043）。在男性中未观察到该变异的关联。内含子5号变异的女性携带者的体重指数高于常见等位基因纯合子女性（分别为23.8±3.8 kg/m2和22.4±3.4 kg/m2，P=0.031）。单倍型分析后观察到类似结果。以HDL-C、LDL-C和体重指数为因变量，年龄、性别和每个基因变异为预测因子进行多元回归分析也得到了类似结果。与LDL-C和HDL-C的关联均表明，SR-BI可能在人类两种脂蛋白类别的代谢中起作用。
