Lima John J, Feng Hua, Duckworth Laurie, Wang Jianwei, Sylvester James E, Kissoon Niranjan, Garg Hardesh
Pharmacogenetics Center, Nemours Children's Clinic, Jacksonville, FL 32207, USA.
Metabolism. 2007 Jun;56(6):757-65. doi: 10.1016/j.metabol.2007.01.007.
Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)-adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 white men and women (age, 18-49 years) to participate in this case-control genetic association study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Associations between genotype and body mass index (BMI), percentage of body fat (by measuring skinfold thickness in 7 different sites), fasting (12-hour) plasma glucose, insulin, potassium concentrations, glycated hemoglobin, and insulin resistance (homeostasis model assessment [HOMA(IR)] score) were performed. Among whites, the ADRB1 Arg389-->Gly variant associated with insulin concentrations and HOMA(IR): mean +/- SD values for insulin and HOMA(IR) in Arg389 homozygotes and carriers of the Gly were 10 +/- 7.0 and 12 +/- 9.4 micro IU/mL (P = .02) and 2.1 +/- 1.7 and 2.6 +/- 2.2 (P = .057), respectively. Systolic blood pressure was higher in whites for carriers of the ADBR1 Ser49 compared to Gly49 homozygotes (124 +/- 12.6 vs 119 +/- 11.3 mm Hg, respectively; P = .02). Subsequent analysis revealed that these associations were attributable to a higher BMI among obese participants. The ADRA2A G1780A SNP associated with BMI and percentage of body fat in African Americans (P = .05). Interactions were detected between ADRA2A C-1291G and ADRB2 Gln27-->Glu variants for obesity in African Americans and between ADRA2A C-1291G SNP and ADBR1 haplotype for obesity in whites. We conclude that common SNPs in adrenergic receptor genes may be important susceptibility loci for obesity and related alterations. Because of the limited size of our populations, our results should be interpreted with caution and should be replicated in larger populations.
由于儿茶酚胺在能量消耗和脂肪分解中发挥作用，参与儿茶酚胺功能调节的基因可能在肥胖中起重要作用。为了确定β₁-肾上腺素能受体（ADRB1）、β₂-肾上腺素能受体（ADRB2）、β₃-肾上腺素能受体（ADRB3）和α₂-肾上腺素能受体（ADRA2A）基因中的常见单核苷酸多态性（SNP）是否与肥胖和代谢改变相关，我们招募了74名健康的非裔美国人和161名白种男性和女性（年龄18 - 49岁）参与这项病例对照基因关联研究。通过聚合酶链反应和限制性片段长度多态性确定基因型。对基因型与体重指数（BMI）、体脂百分比（通过测量7个不同部位的皮褶厚度）、空腹（12小时）血糖、胰岛素、钾浓度、糖化血红蛋白和胰岛素抵抗（稳态模型评估[HOMA(IR)]评分）之间的关联进行了分析。在白种人中，ADRB1基因的Arg389→Gly变异与胰岛素浓度和HOMA(IR)相关：Arg389纯合子和Gly携带者的胰岛素和HOMA(IR)的均值±标准差分别为10±7.0和12±9.4微国际单位/毫升（P = 0.02）以及2.1±1.7和2.6±2.2（P = 0.057）。与Gly49纯合子相比，ADBR1基因Ser49携带者的白种人收缩压更高（分别为124±12.6与119±11.3毫米汞柱；P = 0.02）。后续分析表明，这些关联归因于肥胖参与者中较高的BMI。ADRA2A基因的G1780A SNP与非裔美国人的BMI和体脂百分比相关（P = 0.05）。在非裔美国人中检测到ADRA2A基因C - 1291G与ADRB2基因Gln27→Glu变异之间以及在白种人中检测到ADRA2A基因C - 1291G SNP与ADBR1单倍型之间存在肥胖相关的相互作用。我们得出结论，肾上腺素能受体基因中的常见SNP可能是肥胖及相关改变的重要易感位点。由于我们研究人群规模有限，我们的结果应谨慎解读，并应在更大规模人群中进行重复验证。
