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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.
摘要：
简介：Bardet-Biedl综合征（BBS）是一种罕见的常染色体隐性遗传性疾病，具有视网膜营养不良的临床特征，肥胖，后轴多指，肾脏异常,学习障碍,性腺功能减退,和泌尿生殖系统异常。然而，以前对BBS杂合携带者表型性状的研究没有定论。我们研究的目的是调查与台湾人群中的非携带者相比，BBS杂合性对携带者的影响。材料和方法：本研究遵循基于医院的病例对照设计。我们使用台湾生物库版本2（TWBv2）阵列来识别与BBS相关的三个特定基因座（rs773862084，rs567573386和rs199910690）。总的来说,716例患者被纳入病例组，并将它们与2,864名缺乏BBS等位基因的患者的对照组进行比较。以1:4的比例通过性别和年龄匹配选择对照组。使用逻辑回归模型评估BBS相关基因座与共病之间的关联。结果：我们发现BBS杂合携带者表现出与BMI水平升高的显著关联，尤其是MKS1中的变异体rs199910690(p=0.0037)。携带者组合并症的患病率不高于非携带者组。此外,生化数据的平均值没有显着差异，除了肌酐水平。此外，我们进行了一项基于BMI的分析,以确定慢性肾脏病(CKD)的特定危险因素.我们的发现表明，携带BBS2rs773862084变异的CA/AA基因型或MKS1rs199910690变异的CT/TT基因型的个体显示出发展CKD的风险降低，不管他们的BMI水平。当按BMI水平分层时，具有MKS1rs199910690变体的肥胖男性和具有BBS2rs773862084变体的肥胖女性与CKD发展呈负相关.结论：我们发现，除了与超重和肥胖的关系，杂合BBS突变似乎不会增加个体对合并症和代谢性疾病的易感性。为了更全面地了解与Bardet-Biedl综合征（BBS）相关的遗传易感性，需要进一步的研究。
