Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Oral Epidemiology, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Gene. 2020 Dec 15;762:145019. doi: 10.1016/j.gene.2020.145019. Epub 2020 Aug 2.
Dyslipidemia is a well-established risk factor for cardiovascular disease. Experimental studies have reported that peroxisome proliferator-activated receptor γ (PPAR-γ) regulates adipocyte differentiation, lipid storage, and glucose metabolism. Therefore, we examined the associations between PPAR-γ polymorphisms (rs1801282, rs3856806, rs12497191, rs1151999, and rs1152003) and serum lipids in two cross-sectional studies. In the Shizuoka area of the Japan Multi-Institutional Collaborative Cohort Study, we examined 4,952 participants (3,356 men and 1,596 women) in a baseline survey and 2,245 participants (1,550 men and 695 women) in a second survey 5 years later. Outcome measures were the prevalence of dyslipidemia (low-density lipoprotein-cholesterol [LDL-C] ≥ 140 mg/dl, high-density lipoprotein-cholesterol < 40 mg/dl, triglycerides ≥ 150 mg/dl, and/or use of cholesterol-lowering drugs) and the prevalence of high LDL-C (LDL-C ≥ 140 mg/dl and/or use of cholesterol-lowering drugs). Multivariate odds ratios (ORs) were estimated by using unconditional logistic regression models. A total of 2,114 and 1,431 individuals (42.7% and 28.9%) had dyslipidemia and high LDL-C in the baseline survey, respectively, as did 933 and 716 (41.6% and 31.9%), respectively, in the second survey. In the baseline study, compared with major allele homozygotes, minor allele homozygotes of rs3856806 and rs12497191 had a 42% (OR, 0.58; 95% confidence interval (CI), 0.39-0.85) and 23% (OR, 0.77; 95% CI, 0.60-0.99) lower risk of dyslipidemia, respectively, after adjustment for potential confounding factors. In addition, minor allele homozygotes of rs3856806 had a 45% (OR, 0.55; 95% CI, 0.35-0.86) lower risk of high LDL-C. Similar risk reductions were found in the second survey. In conclusion, rs3856806 and rs12497191 polymorphisms may be related to a lower risk of dyslipidemia and high LDL-C.
血脂异常是心血管疾病的一个明确的危险因素。实验研究表明，过氧化物酶体增殖物激活受体 γ（PPAR-γ）调节脂肪细胞分化、脂质储存和葡萄糖代谢。因此，我们在两项横断面研究中检验了 PPAR-γ 多态性（rs1801282、rs3856806、rs12497191、rs1151999 和 rs1152003）与血清脂质之间的关系。在日本多机构合作队列研究的静冈地区，我们在基线调查中检查了 4952 名参与者（3356 名男性和 1596 名女性）和第二次调查中的 2245 名参与者（1550 名男性和 695 名女性），随访时间为 5 年。结果测量为血脂异常（低密度脂蛋白胆固醇 [LDL-C]≥140mg/dl、高密度脂蛋白胆固醇＜40mg/dl、甘油三酯≥150mg/dl 和/或使用降胆固醇药物）和高 LDL-C（LDL-C≥140mg/dl 和/或使用降胆固醇药物）的患病率。使用无条件逻辑回归模型估计多变量比值比（OR）。基线调查中分别有 2114 人和 1431 人（42.7%和 28.9%）患有血脂异常和高 LDL-C，第二次调查中分别有 933 人和 716 人（41.6%和 31.9%）患有血脂异常和高 LDL-C。在基线研究中，与主要等位基因纯合子相比，rs3856806 和 rs12497191 的次要等位基因纯合子患血脂异常的风险分别降低 42%（OR，0.58；95%置信区间 [CI]，0.39-0.85）和 23%（OR，0.77；95%CI，0.60-0.99），调整潜在混杂因素后。此外，rs3856806 的次要等位基因纯合子患高 LDL-C 的风险降低 45%（OR，0.55；95%CI，0.35-0.86）。在第二次调查中也发现了类似的风险降低。综上所述，rs3856806 和 rs12497191 多态性可能与血脂异常和高 LDL-C 的低风险相关。
