Mokuno Junichiro, Hishida Asahi, Morita Emi, Sasakabe Tae, Hattori Yuta, Suma Shino, Okada Rieko, Kawai Sayo, Naito Mariko, Wakai Kenji
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Endocr J. 2015;62(6):543-9. doi: 10.1507/endocrj.EJ14-0577. Epub 2015 Apr 15.
Among polymorphisms in ATP-binding cassette transporter A1 (ABCA1) gene, the available evidence demonstrates that the ABCA1 R219K polymorphism (G1051A, rs2230806) K allele is associated with a higher high-density lipoprotein cholesterol (HDL- C) level and may play a protective role against coronary artery disease (CAD) risk in Asians and Caucasians. The findings from many underpowered studies from Asian countries (n=71-597), however, still remain inconsistent. The objective of this study was to overcome the limitations of previous studies in Asia and provide solid epidemiologic evidence. Subjects were participants of a cohort study, who visited the Daiko Medical Center in Nagoya, Japan. The cohort study belongs to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). In the Daiko Study, 5,133 participants (1,458 men and 3,675 women) aged 35-69 years enrolled from 2008 through 2010 were eligible for the analyses. The ABCA1 polymorphism was genotyped by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. Among all the subjects, the genotype frequencies were 23.9% (n=1,225) for RR, 49.3% (n=2,532) for RK, and 26.8% (n=1,376) for KK, which was in Hardy-Weinberg's equilibrium (P =0.36). Background characteristics did not significantly differ among the genotypes including alcohol and tobacco use. The mean ± SD of HDL-C concentration was higher in men and women with RK or KK genotype than those with RR, although the difference between these genotypes was not statistically significant in both sexes (P =0.31 in men and 0.26 in women by ANOVA). In the multiple linear regression analysis to estimate the independent effects of the R219K polymorphism on HDL-C level, however, the number of K allele was significantly correlated with an increased level of HDL-C (trend P=0.033). Those with the KK genotype showed a significantly higher HDL-C concentration compared with those with the RR genotype by a mean of 1.18 mg/dL. The R219K polymorphism of ABCA1 independently associated with serum level of HDL-C in a large Japanese population.
在ATP结合盒转运体A1（ABCA1）基因的多态性中，现有证据表明，ABCA1 R219K多态性（G1051A，rs2230806）的K等位基因与较高的高密度脂蛋白胆固醇（HDL-C）水平相关，并且可能在亚洲人和高加索人中对冠状动脉疾病（CAD）风险起到保护作用。然而，来自亚洲国家的许多样本量不足的研究（样本量n = 71 - 597）结果仍不一致。本研究的目的是克服亚洲以往研究的局限性，并提供确凿的流行病学证据。研究对象是队列研究的参与者，他们前往日本名古屋的大佛医疗中心就诊。该队列研究属于日本多机构合作队列研究（J-MICC研究）。在大佛研究中，2008年至2010年纳入的年龄在35 - 69岁的5133名参与者（1458名男性和3675名女性）符合分析条件。ABCA1多态性通过两对引物对抗聚合酶链反应（PCR-CTPP）方法进行基因分型。在所有受试者中，RR基因型频率为23.9%（n = 1225），RK基因型频率为49.3%（n = 2532），KK基因型频率为26.8%（n = 1376），处于哈迪-温伯格平衡（P = 0.36）。包括饮酒和吸烟情况在内的背景特征在各基因型之间无显著差异。RK或KK基因型的男性和女性的HDL-C浓度均值±标准差高于RR基因型者，尽管在两性中这些基因型之间的差异均无统计学意义（方差分析，男性P = 0.31，女性P = 0.26）。然而，在估计R219K多态性对HDL-C水平的独立影响的多元线性回归分析中，K等位基因数量与HDL-C水平升高显著相关（趋势P = 0.033）。与RR基因型者相比，KK基因型者的HDL-C浓度显著更高，平均高1.18mg/dL。在一大群日本人群中，ABCA1的R219K多态性与HDL-C血清水平独立相关。
