. 2022 Mar 10:13:808956.

doi: 10.3389/fendo.2022.808956. eCollection 2022.

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

Hui Wang¹, Jing Li^{1

2

3}, Junhong Leng⁴, Weiqin Li⁴, Jinnan Liu¹, Xiaoyan Yan⁵, Zhijie Yu⁶, Gang Hu⁷, Ronald C W Ma⁸, Zhongze Fang^{2

3

9}, Ying Wang¹⁰, Xilin Yang^{1

2

3}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
² Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China.
³ Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China.
⁴ Project Office, Tianjin Women and Children's Health Center, Tianjin, China.
⁵ School of Public Health, Shanxi Medical University, Shanxi, China.
⁶ Population Cancer Research Program and Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
⁷ Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States.
⁸ Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁹ Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China.
¹⁰ Scientific Research Platform of the Second School of Clinical Medicine & Key Laboratory of 3D Printing Technology in Stomatology, Guangdong Medical University, Dongguan, China.

PMID: 35360068
PMCID: PMC8960111
DOI: 10.3389/fendo.2022.808956

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

Hui Wang et al. Front Endocrinol (Lausanne). 2022.

. 2022 Mar 10:13:808956.

doi: 10.3389/fendo.2022.808956. eCollection 2022.

Authors

Hui Wang¹, Jing Li^{1

2

3}, Junhong Leng⁴, Weiqin Li⁴, Jinnan Liu¹, Xiaoyan Yan⁵, Zhijie Yu⁶, Gang Hu⁷, Ronald C W Ma⁸, Zhongze Fang^{2

3

9}, Ying Wang¹⁰, Xilin Yang^{1

2

3}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
² Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China.
³ Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China.
⁴ Project Office, Tianjin Women and Children's Health Center, Tianjin, China.
⁵ School of Public Health, Shanxi Medical University, Shanxi, China.
⁶ Population Cancer Research Program and Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
⁷ Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States.
⁸ Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁹ Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China.
¹⁰ Scientific Research Platform of the Second School of Clinical Medicine & Key Laboratory of 3D Printing Technology in Stomatology, Guangdong Medical University, Dongguan, China.

PMID: 35360068
PMCID: PMC8960111
DOI: 10.3389/fendo.2022.808956

Abstract

Aims: The study aimed to explore additive interactions of CDKAL1 rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated via increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0.

Methods: A 1:1 age-matched study nested in a prospective cohort of pregnant women (207 pairs) was organized in Tianjin, China. Additive interactions were used to test interaction effects while mediation analyses and Sobel tests were used to test mediation effects of LPC18:0 and SFA16:0 between copresence of rs7747752 and low GUDCA/DCA, and GDM risk.

Results: The CDKAL1 rs7747752 was associated with GDM (P<0.05). The rs7747752 C polymorphism markedly enhanced ORs of low GUDCA from 4.04 (0.72-22.8) to 9.02 (1.63-49.7) and low DCA from 1.67 (0.68-4.11) to 4.24 (1.84-9.76), both with significant additive interactions. Further adjustment for LPC18:0 attenuated the interactive effects of rs7747752 and low DCA, with a significant mediation effect (P=0.003). High SFA16:0 did not mediate the interactive effects of rs7747752 and low DCA/GUDCA on GDM risk.

Conclusions: The CDKAL1 rs7747752 C carrier status and low GUDCA/DCA had significant additive interactions on the risk of GDM with the effect from interaction with DCA being partially mediated via increasing LPC18:0.

Keywords: CDKAL1; deoxycholic acid; gestational diabetes mellitus; glycoursodeoxycholic acid; rs7747752.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Cited by

Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls.
Grupe K, Scherneck S. Grupe K, et al. Int J Mol Sci. 2023 Mar 22;24(6):5982. doi: 10.3390/ijms24065982. Int J Mol Sci. 2023. PMID: 36983056 Free PMC article. Review.
Elevated Bile Acid Is Associated with Worsened Impaired Glucose Homeostasis in Pancreatic Ductal Adenocarcinoma Patients with Extrahepatic Cholestasis through Increased Hepatic Insulin Clearance.
Yang J, Tan C, Zheng Z, Wang X, Liu X, Chen Y. Yang J, et al. J Clin Med. 2023 Mar 17;12(6):2352. doi: 10.3390/jcm12062352. J Clin Med. 2023. PMID: 36983352 Free PMC article.
Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus.
Suthon S, Tangjittipokin W. Suthon S, et al. Int J Mol Sci. 2024 Feb 7;25(4):2039. doi: 10.3390/ijms25042039. Int J Mol Sci. 2024. PMID: 38396716 Free PMC article. Review.

References

1. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. . IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group’s Criteria. Diabetes Res Clin Pract (2022) 183:109050. doi: 10.1016/j.diabres.2021.109050 - DOI - PubMed
1. Song C, Lyu Y, Li C, Liu P, Li J, Ma RC, et al. . Long-Term Risk of Diabetes in Women at Varying Durations After Gestational Diabetes: A Systematic Review and Meta-Analysis With More Than 2 Million Women. Obes Rev (2018) 19(3):421–9. doi: 10.1111/obr.12645 - DOI - PubMed
1. Gao M, Cao S, Li N, Liu J, Lyu Y, Li J, et al. . Risks of Overweight in the Offspring of Women With Gestational Diabetes at Different Developmental Stages: A Meta-Analysis With More Than Half a Million Offspring. Obes Rev (2022) 23(3):e13395. doi: 10.1111/obr.13395 - DOI - PubMed
1. Li N, Yang Y, Cui D, Li C, Ma RCW, Li J, et al. . Effects of Lifestyle Intervention on Long-Term Risk of Diabetes in Women With Prior Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Obes Rev (2021) 22(1):e13122. doi: 10.1111/obr.13122 - DOI - PubMed
1. Li J, Liu J, Zhang C, Liu G, Leng J, Wang L, et al. . Effects of Lifestyle Intervention of Maternal Gestational Diabetes Mellitus on Offspring Growth Pattern Before Two Years of Age. Diabetes Care (2021) 44(3):e42–4. doi: 10.2337/dc20-2750 - DOI - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

Affiliations

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

Authors

Affiliations

Abstract

Conflict of interest statement

Similar articles

Cited by

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Abstract

Conflict of interest statement

Similar articles

Cited by

References

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources