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突尼斯女性脂联素基因变异、血清水平与2型糖尿病风险之间的关联研究:基于体重指数分层的见解

Association study between adiponectin gene variants, serum levels and the risk of type 2 diabetes in Tunisian women: Insights from BMI stratification.

作者信息

Sarray Sameh, Ezzidi Intissar, Moussa Saif, Abdennebi Hassen Ben, Mtiraoui Nabil

机构信息

College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain; Faculty of Sciences, University of Tunis EL Manar, Tunis, Tunisia.

Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia; Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia.

出版信息

Cytokine. 2024 Sep;181:156695. doi: 10.1016/j.cyto.2024.156695. Epub 2024 Jul 16.

DOI:10.1016/j.cyto.2024.156695
PMID:39018944
Abstract

Although prior studies have shown that adiponectin synthesis is genetically determined and that its levels influence susceptibility to T2D, the results in this regard have been inconsistent. This study aims, to investigate the relationship between adiponectin gene variants with the risk of developing T2D among Tunisian women and in relation to their BMI status. A cohort of 491 Tunisian T2D women and 373 non-diabetic subjects participated in the study. Nine ADIPOQ variants namely rs16861194, rs17300539, rs266729, rs822395, rs822396, rs2241766, rs1501299, rs2241767 and rs3774261 were selected and genotyped using the TaqMan® SNP genotyping assay. Fasting serum adiponectin levels were quantified using ELISA. The results showed that only the rs17300539 variant exhibited a significant association with the risk of T2D. However, upon considering T2D group stratification based on BMI (normal weight [18-24.99 Kg/m], overweight [25-29.99 Kg/m] and obese [30-34.99 Kg/m]), the ADIPOQ rs2241766 variant emerged as a contributing risk factor for increased BMI in obese women with T2D. Linear regression analysis revealed that the minor allele (A), (GA) and (AA) genotypes of rs17300539 as well as the (G) allele and (GG) genotype of rs2241766 were significantly associated with hypoadiponectinemia in T2D subjects. Two haplotypes namely GGCAATGAA and AGCCGTGGA, were identified as conferring a higher risk of T2D with the GGCAATGAA haplotype also correlating with hypoadiponectinemia. Our study underscores the importance of the rs17300539 variant and the GGCAATGAA haplotype in the risk of T2D and hypoadiponectinemia. Additionally, the presence of the rs2241766 variant highlights its association with 'diabesity' and hypoadiponectinemia among Tunisian T2D women.

摘要

尽管先前的研究表明脂联素的合成是由基因决定的,其水平会影响患2型糖尿病的易感性,但这方面的研究结果并不一致。本研究旨在调查突尼斯女性中脂联素基因变异与患2型糖尿病风险之间的关系,并探讨其与体重指数(BMI)状态的关联。491名突尼斯2型糖尿病女性和373名非糖尿病受试者参与了该研究。选择了9个ADIPOQ基因变异,即rs16861194、rs17300539、rs266729、rs822395、rs822396、rs2241766、rs1501299、rs2241767和rs3774261,并使用TaqMan®SNP基因分型检测法进行基因分型。采用酶联免疫吸附测定法(ELISA)对空腹血清脂联素水平进行定量分析。结果显示,只有rs17300539变异与2型糖尿病风险存在显著关联。然而,在根据BMI对2型糖尿病组进行分层(正常体重[18 - 24.99 Kg/m²]、超重[25 - 29.99 Kg/m²]和肥胖[30 - 34.99 Kg/m²])后,ADIPOQ基因的rs2241766变异成为患有2型糖尿病的肥胖女性BMI增加的一个风险因素。线性回归分析显示,rs17300539的次要等位基因(A)、(GA)和(AA)基因型以及rs2241766的(G)等位基因和(GG)基因型与2型糖尿病患者的低脂联素血症显著相关。鉴定出两种单倍型,即GGCAATGAA和AGCCGTGGA,它们具有更高的2型糖尿病风险,其中GGCAATGAA单倍型也与低脂联素血症相关。我们的研究强调了rs17300539变异和GGCAATGAA单倍型在2型糖尿病风险和低脂联素血症中的重要性。此外,rs2241766变异的存在凸显了其与突尼斯2型糖尿病女性的“糖尿病肥胖症”和低脂联素血症的关联。

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