Abstract
Purpose
Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in women of childbearing age, and many patients with PCOS have obesity and insulin resistance (IR). Although obesity is related to an increased risk of IR, in clinical practice, PCOS patients exhibit different effects on improving insulin sensitivity after weight loss. Therefore, in the present study, we aimed to examine the moderating effect of polymorphisms of mtDNA in the D-loop region on the associations of body mass index (BMI) with the homeostasis model assessment of insulin resistance index (HOMA-IR) and pancreatic β cell function index (HOMA-β) among women with PCOS.
Methods
Based on a cross-sectional study, women with PCOS were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from 2015 to 2018. A total of 520 women who were diagnosed with PCOS based on the revised 2003 Rotterdam criteria were included in the study. Peripheral blood was collected from these patients, followed by DNA extraction, PCR amplification, and sequencing at baseline. HOMA-IR and HOMA-β were calculated according to blood glucose-related indices. Moderating effect models were performed with BMI as an independent variable, polymorphisms of mtDNA in the D-loop region as moderators, and ln (HOMA-IR) and ln (HOMA-β) as dependent variables. To verify the stability of moderating effect, sensitivity analysis was performed with the quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose/fasting insulin (G/I), and fasting insulin as dependent variables.
Results
BMI was positively associated with ln (HOMA-IR) and ln (HOMA-β) (β = 0.090, p < 0.001; β = 0.059, p < 0.001, respectively), and the relationship between BMI and ln (HOMA-IR) or ln (HOMA-β) was moderated by the polymorphisms of mtDNA in the D-loop region. Compared with the respective wild-type, the variant -type of m.16217 T > C enhanced the association between BMI and HOMA-IR, while the variant-type of m.16316 A > G weakened the association. On the other hand, the variant-type of m.16316 A > G and m.16203 A > G weakened the association between BMI and HOMA-β, respectively. The results of QUICKI and fasting insulin as dependent variables were generally consistent with HOMA-IR, and the results of G/I as dependent variables were generally consistent with HOMA-β.
Conclusion
Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-β among women with PCOS.
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Data Availability
The authors do not have permission to share data.
Change history
17 July 2023
A Correction to this paper has been published: https://doi.org/10.1007/s10815-023-02884-y
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Acknowledgements
The authors are grateful to the Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, for the technical support during our experiments.
Funding
This work was supported by the National Key Research and Development Program (2021YFC2700901, 2018YFC1004201), the National Natural Science Foundation of China (NSFC-82173532, NSFC-U20A20350, NSFC-81971455, NSFC-81871216, and NSFC-81803260), the Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province (gxyq2021173), and the Postdoctoral Research Foundation of China (2021M700181).
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Shitao He: methodology, formal analysis, data curation, writing – original draft. Dongmei Ji: methodology, formal analysis, visualization, writing – original draft, funding acquisition. Yajing Liu: methodology, investigation. Xiaohong Deng: methodology, formal analysis. Weiwei Zou: methodology, data curation. Dan Liang: methodology, data curation. Yinan Du: methodology. Kai Zong: Methodology. Tingting Jiang: methodology. Mengzhu Li: methodology. Dongyang Zhang: methodology. Xinyu Yue: methodology. Fangbiao Tao: conceptualization, project administration, funding acquisition, resources, supervision, writing – review and editing. Yunxia Cao: conceptualization, funding acquisition, project administration, writing – review and editing. Chunmei Liang: conceptualization, funding acquisition, supervision, writing – review and editing. All authors have read and approved the final version of the manuscript.
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He, S., Ji, D., Liu, Y. et al. Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-β among women with polycystic ovary syndrome: a cross-sectional study. J Assist Reprod Genet 40, 1983–1993 (2023). https://doi.org/10.1007/s10815-023-02843-7
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DOI: https://doi.org/10.1007/s10815-023-02843-7