Background: HNF1A-MODY is a monogenic form of diabetes caused by variants in the HNF1A gene. Different HNF1A variants are associated with differences in age of disease onset, but other factors are postulated to influence this trait. Here, we searched for genetic variants influencing age of HNF1A-MODY onset.
Methods: Blood samples from 843 HNF1A-MODY patients from Czech Republic, France, Poland, Slovakia, the UK and the US were collected. A validation set consisted of 121 patients from the US. We conducted a genome-wide association study in 843 HNF1A-MODY patients. Samples were genotyped using Illumina Human Core arrays. The core analysis was performed using the GENESIS package in R statistical software. Kinship coefficients were estimated with the KING and PC-Relate algorithms. In the linear mixed model, we accounted for year of birth, sex, and location of the HNF1A causative variant.
Results: A suggestive association with age of disease onset was observed for rs2305198 (p = 2.09E-07) and rs7079157 (p = 3.96E-06) in the HK1 gene, rs2637248 in the LRMDA gene (p = 2.44E-05), and intergenic variant rs2825115 (p = 2.04E-05). Variant rs2637248 reached nominal significance (p = 0.019), while rs7079157 (p = 0.058) and rs2825115 (p = 0.068) showed suggestive association with age at diabetes onset in the validation set.
Conclusions: rs2637248 in the LRMDA gene is associated with age at diabetes onset in HNF1A-MODY patients.
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http://dx.doi.org/10.1186/s10020-022-00542-0 | DOI Listing |
Indian J Endocrinol Metab
November 2024
Department of Genetics, MedGenome Labs, Tamil Nadu, India.
Introduction: Maturity-onset diabetes of the young (MODY) is a rare group of disorders characterised by impaired functions or development of pancreatic islets and monogenic diabetes at a young age. Diagnosing MODY can be rewarding for both clinicians and patients as it can change the management from generic to targeted therapy.
Methods: This study reports the retrospective analysis of data collected from four clinics between March 2016 and February 2023 from Lucknow, a city in northern India.
J Med Case Rep
October 2024
National Obesity Centre and the Endocrinology and Metabolic Diseases Unit, Yaoundé Central Hospital, Yaoundé, Cameroon.
Background: Maturity onset diabetes of the young is one of the commonest causes of monogenic diabetes and can easily be mistaken for type 1 diabetes. A diagnosis of maturity onset diabetes of the young can have direct implications for genetic counseling, family screening, and precision diabetes treatment. However, the cost of genetic testing and identifying individuals to test are the main challenges for diagnosis and management in sub-Saharan Africa.
View Article and Find Full Text PDFExp Clin Endocrinol Diabetes
November 2024
Department of Internal Medicine, Gastroenterology and Diabetology, Franziskus Hospital Harderberg, Niels Stensen Hospitals, Georgsmarienhütte, Germany.
J Clin Endocrinol Metab
August 2024
Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Center, Beijing, 100044, China.
Context: Rare variants in HNF1A cause both maturity onset diabetes of the young 3 (HNF1A-MODY) and reduced serum C reactive protein (CRP) levels. Common variants of HNF1A are associated with serum CRP and type 2 diabetes, but inconsistently with cardiovascular disease (CVD).
Objective: Our study aimed to investigate the association of low CRP-alleles in HNF1A with CVD and indirectly evaluate the CVD risk of HNF1A-MODY patients because of unavailability of enough cases to study their clinical outcomes.
Front Endocrinol (Lausanne)
March 2024
Pediatric Department, King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Maturity-onset diabetes of the young (MODY) is a grouping of monogenic disorders. It is characterized by dominantly inherited, non-insulin-dependent diabetes. MODY is relatively rare, encompassing up to 3.
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