Pinnaro Catherina T, Zimmerman Blake Irvin, Ryckman Kelli K, Darbro Benjamin W, Norris Andrew W
Division of Endocrinology and Diabetes, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USA.
Horm Res Paediatr. 2024 Nov 18:1-9. doi: 10.1159/000542677.
The cause of increased diabetes mellitus (DM) risk in individuals with Turner syndrome (TS) is poorly understood. Parent-of-origin effects related to whether the maternal or paternal X chromosome (Xchr) remains intact have been found for several TS phenotypes, including hypercholesterolemia. Therefore, Xchr parent-of-origin may impact DM risk in TS. The aim of this study was to determine whether Xchr parent-of-origin affects glycaemia, as measured by oral glucose tolerance test (OGTT), in TS.
A total of 81 individuals with 45,X karyotype from the TS: Genotype Phenotype study had Xchr parent-of-origin assessment and completed a 3-h OGTT. Parallel-slopes multiple linear regression modeling was used to test whether Xchr parent-of-origin, age, and/or body mass index (BMI) significantly predicted incremental area under the glucose curve (iAUC). A second analysis included 62 additional individuals with 45,X mosaicism.
All three factors predicted iAUC glucose in the 81 individuals with 45,X karyotype (age: β = 0.36, p = 0.0004; BMI: β = 0.33, p = 0.001; Xchr parent-of-origin: β = 0.21; p = 0.01). The overall model remained statistically significant when including individuals with 45,X mosaicism, but Xchr parent-of-origin was no longer significant.
Maternal Xchr monosomy predicts higher glucose concentration than paternal Xchr monosomy in response to oral glucose in 45,X individuals. This effect is obscured when including individuals who are mosaic, potentially due to the presence of both parent Xchrs in the non-45,X cell line.
特纳综合征（TS）患者患糖尿病（DM）风险增加的原因尚不清楚。已发现与母源或父源X染色体（Xchr）是否完整相关的亲源效应存在于包括高胆固醇血症在内的几种TS表型中。因此，Xchr亲源可能会影响TS患者患DM的风险。本研究的目的是确定Xchr亲源是否会影响TS患者口服葡萄糖耐量试验（OGTT）所测得的血糖水平。
来自TS：基因型-表型研究的81名核型为45,X的个体进行了Xchr亲源评估，并完成了3小时的OGTT。采用平行斜率多元线性回归模型来检验Xchr亲源、年龄和/或体重指数（BMI）是否能显著预测葡萄糖曲线下增量面积（iAUC）。第二项分析纳入了另外62名具有45,X嵌合体的个体。
在81名核型为45,X的个体中，所有这三个因素均能预测iAUC葡萄糖水平（年龄：β = 0.36，p = 0.0004；BMI：β = 0.33，p = 0.001；Xchr亲源：β = 0.21；p = 0.01）。当纳入具有45,X嵌合体的个体时，总体模型仍具有统计学意义，但Xchr亲源不再具有显著性。
在45,X个体中，母源Xchr单体型比父源Xchr单体型对口服葡萄糖的反应预测出更高的葡萄糖浓度。当纳入嵌合体个体时，这种效应被掩盖，可能是由于在非45,X细胞系中同时存在父母双方的Xchrs。
