Department of Endocrinology, Nanjing General Hospital of Nanjing Command, Jiangsu Province, PR China.
J Endocrinol Invest. 2012 Oct;35(9):859-65. doi: 10.3275/8238. Epub 2012 Jan 30.
The leptin receptor (LEPR) is an important regulator of leptin activity and resistance. Several single nucleotide polymorphisms (SNP) of LEPR have been linked to diseases accompanying obesity and/or obesity-related diseases in different populations. However, the results from published studies remain inconsistent rather than conclusive.
To investigate whether LEPR SNP are associated with essential hypertension and related metabolic traits in Chinese subjects.
A total of 544 Chinese patients with hypertension and 357 non-hypertensive subjects were screened. The genotypes of LEPR polymorphisms were determined by PCR-restriction fragment length polymorphism methods. Demographic and biochemical characteristics including waist circumference, waist-to-hip ratio, body mass index (BMI), lipids profiles, glucose metabolism, and leptin levels were obtained for analysis.
This case-control study showed associations between the frequencies of AA genotype and A allele of Gln223Arg and hypertension (p=0.029, p=0.002, respectively). Furthermore, the Gln223Arg polymorphism was significantly associated with plasma leptin levels (p<0.001), while no correlations between Lys109Arg SNP and hypertension were found. Multivariate logistic regression analysis evidenced that A allele carriers of Gln223Arg (AA+AG) showed higher risks of hypertension than GG carriers after adjustment of age and sex (adjusted odds ratio: 1.549, 95% confidence interval: 1.031- 2.036, p=0.035). BMI, fasting serum insulin, oral glucose tolernace test (OGTT)-2h glucose, serum leptin, as well as LDL-cholesterol (LDL-C) levels were also independent risk factors of hypertension in this population. In addition, significant associations were observed between the Gln223Arg and Lys109Arg SNP and serum total cholesterol, LDL-C, and fasting plasma glucose levels in hypertensive patients. Besides, A allele of Gln223Arg had raised diastolic blood pressure, compared with GG carriers (p=0.001). While variance of Lys109Arg was associated with waist-to-hip ratio, OGTT-2h glucose, and homeostasis model assessment of insulin resistance (p<0.05).
LEPR polymorphisms may be a marker for susceptibility to essential hypertension in Chinese subjects, and be involved in the development of several features including dyslipidemia and impaired glucose regulation in hypertension subjects.
瘦素受体（LEPR）是瘦素活性和抵抗的重要调节剂。几种 LEPR 的单核苷酸多态性（SNP）已被证明与不同人群中伴随肥胖和/或肥胖相关疾病的疾病有关。然而，已发表的研究结果仍然不一致，而不是结论性的。
探讨 LEPR SNP 是否与中国人群的原发性高血压及相关代谢特征有关。
筛选了 544 例高血压患者和 357 例非高血压患者。采用 PCR-限制性片段长度多态性方法检测 LEPR 多态性的基因型。分析了包括腰围、腰臀比、体重指数（BMI）、血脂谱、葡萄糖代谢和瘦素水平在内的人口统计学和生化特征。
这项病例对照研究显示，Gln223Arg 的 AA 基因型和 A 等位基因的频率与高血压有关（p=0.029，p=0.002）。此外，Gln223Arg 多态性与血浆瘦素水平显著相关（p<0.001），而 Lys109Arg SNP 与高血压之间没有相关性。多变量 logistic 回归分析表明，Gln223Arg 的 A 等位基因携带者（AA+AG）在调整年龄和性别后，高血压的风险高于 GG 携带者（调整后的优势比：1.549，95%置信区间：1.031-2.036，p=0.035）。在该人群中，BMI、空腹血清胰岛素、口服葡萄糖耐量试验（OGTT）-2h 血糖、血清瘦素以及 LDL 胆固醇（LDL-C）水平也是高血压的独立危险因素。此外，在高血压患者中，Gln223Arg 和 Lys109Arg SNP 与血清总胆固醇、LDL-C 和空腹血浆葡萄糖水平之间存在显著相关性。此外，Gln223Arg 的 A 等位基因与 GG 携带者相比，舒张压升高（p=0.001）。而 Lys109Arg 的变异与腰臀比、OGTT-2h 血糖和胰岛素抵抗的稳态模型评估有关（p<0.05）。
LEPR 多态性可能是中国人原发性高血压易感性的一个标志物，并与血脂异常和高血压患者葡萄糖调节受损等多种特征的发生有关。
