División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa 86100, Mexico.
Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06520, USA.
Int J Mol Sci. 2024 Sep 21;25(18):10154. doi: 10.3390/ijms251810154.
Latent autoimmune diabetes in adults (LADA) is characterized by the presence of glutamate decarboxylase autoantibodies (GADA). LADA has intermediate features between type 1 diabetes and type 2 diabetes. In addition, genetic risk factors for both types of diabetes are present in LADA. Nonetheless, evidence about the genetics of LADA in non-European populations is scarce. This study aims to perform a genome-wide association study with a phenome-wide association study of LADA in a southeastern Mexican population. We included 59 patients diagnosed with LADA from a previous study and 3121 individuals without diabetes from the MxGDAR/ENCODAT database. We utilized the GENESIS package in R to perform the genome-wide association study (GWAS) of LADA and PLINK for the phenome-wide association study (PheWAS) of LADA features. Nine polymorphisms reach the nominal association level (1 × 10) in the GWAS. The PheWAS showed that rs7305229 is genome-wide and associated with serum GADA levels in our sample ( = 1.84 × 10). rs7305229 is located downstream of the FAIM2 gene; previous reports associate FAIM2 variants with childhood obesity, body mass index, body adiposity measures, lymphocyte CD8+ activity, and anti-thyroid peroxidase antibodies. Our findings reveal that rs7305229 affects the GADA levels in patients with LADA from southeastern Mexico. More studies are needed to determine if this risk genotype exists in other populations with LADA.
成人隐匿性自身免疫性糖尿病(LADA)的特征是存在谷氨酸脱羧酶自身抗体(GADA)。LADA 在 1 型糖尿病和 2 型糖尿病之间具有中间特征。此外,LADA 中存在两种类型糖尿病的遗传风险因素。尽管如此,关于非欧洲人群中 LADA 的遗传学证据仍然很少。本研究旨在对东南墨西哥人群中的 LADA 进行全基因组关联研究和表型全基因组关联研究。我们纳入了先前研究中诊断为 LADA 的 59 名患者和 MxGDAR/ENCODAT 数据库中没有糖尿病的 3121 名个体。我们使用 R 中的 GENESIS 软件包进行 LADA 的全基因组关联研究(GWAS),并使用 PLINK 进行 LADA 特征的表型全基因组关联研究(PheWAS)。GWAS 中有 9 个多态性达到名义关联水平(1×10)。PheWAS 显示 rs7305229 在我们的样本中与血清 GADA 水平呈全基因组关联(=1.84×10)。rs7305229 位于 FAIM2 基因的下游;先前的报告将 FAIM2 变体与儿童肥胖、体重指数、身体脂肪测量、淋巴细胞 CD8+活性和抗甲状腺过氧化物酶抗体联系起来。我们的研究结果表明,rs7305229 影响来自墨西哥东南部的 LADA 患者的 GADA 水平。需要更多的研究来确定这种风险基因型是否存在于其他具有 LADA 的人群中。