ISSN: 1449-1907International Journal of Medical Sciences
Global reach, higher impact
Int J Med Sci 2024; 21(5):784-794. doi:10.7150/ijms.92766 This issue Cite
Research Paper
The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers
1. Division of Pediatric Genetics and Metabolism, Children's Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan.
2. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
3. Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
4. Division of Nephrology, Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.
5. School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
6. Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
7. Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan.
Abstract
Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population.
Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models.
Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development.
Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted
Keywords: Bardet-Biedl syndrome, BBS2 rs773862084, MKS1 rs199910690, heterozygotes, obesity, BMI, CKD
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