Department of Internal Medicine with Respiratory Medicine Center, Sumy State University, Ukraine.
Georgian Med News. 2023 Jul-Aug(340-341):254-258.
The objective of study was to investigate the association between the Gln27Glu polymorphism in the β2-АR gene and body mass index in patients with bronchial asthma with regard to the age of onset. Study included 553 patients with bronchial asthma (BA) and 95 apparently healthy individuals with no individual and family history of asthma symptoms. All of them had previously signed an informed consent form for study participation. The patients were divided into 2 clinical groups depending on the age of BA onset. Group I included 282 patients with late-onset asthma (late-onset asthma phenotype), and Group II included 271 patients with early-onset asthma (early-onset asthma phenotype). There was no significant difference in gender, age, severity, or control level between the groups (р>0.05). BA diagnosis and BA severity were determined according to the GINA recommendations-2016 and its later version. Obesity was diagnosed in accordance with the Order of the Ministry of Health of Ukraine № 574 dated 05.08.2009 and the WHO recommendations (1999), the European Association for the Study of Obesity (EASO, 2016). The Gln27Glu polymorphism in the β2-АR gene (rs1042714) was determined using polymerase chain reaction-restriction fragment length polymorphism analysis. The obtained results were statistically analyzed using SPSS-17 program. No significant difference was established in the distribution of alleles and genotypes for the Gln27Glu polymorphism in the β2-adrenergic receptor gene depending on body mass index (BMI), p=0.1. Obesity relative risk estimation showed a statistically significant correlation related to the dominant (p=0.03) and additive (p=0.04) models of inheritance. The risk of obesity in minor allele carriers (Glu/Glu+Gln/Glu) was 1.75 times higher than that in the major allele homozygotes (р=0.03). No association was observed between the Gln27Glu polymorphism in the β2-AR gene and obesity risk in patients with early-onset bronchial asthma in any model of inheritance. Obesity relative risk estimation in late-onset BA patients showed a statistically significant correlation related to the dominant (p=0.03) and additive (p = 0.001) models of inheritance. The minor allele carriers (Gln/Glu and Glu/Glu genotypes) with late-onset BA had a 1.95 times higher risk of obesity in the dominant model and 1.65 times higher risk of obesity in the additive model vs. the major allele homozygotes. The obtained data indicated that the minor allele carriers of the Gln27Glu polymorphism in the β2-АR gene (both homozygotes and heterozygotes) with late-onset BA had a higher risk of obesity.
研究目的在于探讨β2-肾上腺素能受体(β2-АR)基因 Gln27Glu 多态性与支气管哮喘患者体重指数(BMI)之间的关联,同时考虑哮喘发病年龄。本研究纳入了 553 名支气管哮喘(BA)患者和 95 名无哮喘症状个体和家族史的健康对照者。所有参与者均签署了参与研究的知情同意书。根据 BA 发病年龄,患者被分为 2 个临床组。第 1 组(282 名)为晚发型哮喘(晚发型哮喘表型),第 2 组(271 名)为早发型哮喘(早发型哮喘表型)。2 组间的性别、年龄、严重程度或控制水平无显著差异(p>0.05)。BA 的诊断和严重程度依据 GINA 指南-2016 及其后版本确定。肥胖的诊断符合乌克兰卫生部 2009 年 8 月 5 日第 574 号命令和世界卫生组织(1999 年)、欧洲肥胖研究协会(EASO,2016 年)的建议。采用聚合酶链反应-限制性片段长度多态性分析技术检测β2-AR 基因(rs1042714)Gln27Glu 多态性。使用 SPSS-17 程序对获得的结果进行统计学分析。β2-肾上腺素能受体基因 Gln27Glu 多态性的等位基因和基因型分布与 BMI 无关(p=0.1)。肥胖相对风险的估计显示与显性(p=0.03)和加性(p=0.04)遗传模型相关的具有统计学显著性的相关性。携带次要等位基因(Glu/Glu+Gln/Glu)的个体发生肥胖的风险比主要等位基因纯合子高 1.75 倍(p=0.03)。在任何遗传模型中,β2-AR 基因 Gln27Glu 多态性与早发型支气管哮喘患者的肥胖风险均无相关性。在晚发型 BA 患者中,肥胖相对风险的估计显示与显性(p=0.03)和加性(p=0.001)遗传模型相关的具有统计学显著性的相关性。在显性模型中,携带晚发型 BA 的 Gln27Glu 多态性的次要等位基因(Gln/Glu 和 Glu/Glu 基因型)的个体肥胖风险是主要等位基因纯合子的 1.95 倍;在加性模型中,携带晚发型 BA 的 Gln27Glu 多态性的次要等位基因(Gln/Glu 和 Glu/Glu 基因型)的个体肥胖风险是主要等位基因纯合子的 1.65 倍。这些数据表明,β2-АR 基因 Gln27Glu 多态性的次要等位基因携带者(杂合子和纯合子)发生晚发型 BA 的肥胖风险更高。