Dataset Information

Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population.

ABSTRACT: Background and Objectives: The gut microbiota has been increasingly recognized as a relevant factor associated with metabolic diseases. However, directly measuring the microbiota composition is a limiting factor for several studies. Therefore, using genetic variables as proxies for the microbiota composition is an important issue. Landmark microbiome-host genome-wide association studies (mbGWAS) have identified many SNPs associated with gut microbiota. Our aim was to analyze the association between relevant microbiome-related genetic variants (Mi-RSNPs) and fasting glucose and type 2 diabetes in a Mediterranean population, exploring the interaction with Mediterranean diet adherence. Materials and Methods: We performed a cross-sectional study in a high-cardiovascular-risk Mediterranean population (n = 1020), analyzing the association of Mi-RSNPs (from four published mbGWAS) with fasting glucose and type 2 diabetes. A single-variant approach was used for fitting fasting glucose and type 2 diabetes to a multivariable regression model. In addition, a Mendelian randomization analysis with multiple variants was performed as a sub-study. Results: We obtained several associations between Mi-RSNPs and fasting plasma glucose involving gut Gammaproteobacteria_HB, the order Rhizobiales, the genus Rumminococcus torques group, and the genus Tyzzerella as the top ranked. For type 2 diabetes, we also detected significant associations with Mi-RSNPs related to the order Rhizobiales, the family Desulfovibrionaceae, and the genus Romboutsia. In addition, some Mi-RSNPs and adherence to Mediterranean diet interactions were detected. Lastly, the formal Mendelian randomization analysis suggested combined effects. Conclusions: Although the use of Mi-RSNPs as proxies of the microbiome is still in its infancy, and although this is the first study analyzing such associations with fasting plasma glucose and type 2 diabetes in a Mediterranean population, some interesting associations, as well as modulations, with adherence to the Mediterranean diet were detected in these high-cardiovascular-risk subjects, eliciting new hypotheses.

SUBMITTER: Asensio EM

PROVIDER: S-EPMC9502852 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population.

Asensio Eva M EM Ortega-Azorín Carolina C Barragán Rocío R Alvarez-Sala Andrea A Sorlí José V JV Pascual Eva C EC Fernández-Carrión Rebeca R Villamil Laura V LV Corella Dolores D Coltell Oscar O

Medicina (Kaunas, Lithuania) 20220907 9

<i>Background and Objectives</i>: The gut microbiota has been increasingly recognized as a relevant factor associated with metabolic diseases. However, directly measuring the microbiota composition is a limiting factor for several studies. Therefore, using genetic variables as proxies for the microbiota composition is an important issue. Landmark microbiome-host genome-wide association studies (mbGWAS) have identified many SNPs associated with gut microbiota. Our aim was to analyze the associati ...[more]

PMID: 36143914

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Project description:Background and aimsThe aim of this study is to investigate the association between visit-to-visit variability in fasting plasma glucose (FPG) and the risk of digestive cancers among individuals with and without diabetes.MethodsUsing data from Kailuan cohort, a prospective population-based study, individuals who had at least two measurements of FPG between 2006 and 2012 without prior cancer were included in this study. Four indexes of variability were used, including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average successive variability (ARV). Cox regression was used to evaluate the relationship between the quartiles of FPG variability and digestive cancers.ResultsA total of 98,161 individuals were studied. Over a mean follow-up of 9.32 ± 0.81 years, 1103 individuals developed incident digestive cancer (1.21 per 1000 person-years). Compared to the individuals in the lowest quartile, those in the highest quartile of FPG variability by SD had 38.7% higher risk of developing overall digestive cancers after adjusting for the significant confounders (hazard ratio, 1.387; 95% confidence interval, 1.160-1.659; P = 0.0003). Higher FPG variability was associated with significantly higher risks of colorectal cancer (fully adjusted HR 1.432, 95% CI [1.073-1.912], P = 0.015) and pancreatic cancer (fully adjusted HR 2.105, 95% CI [1.024-4.329], P = 0.043), but not liver cancer (fully adjusted HR 1.427, 95% CI [0.973-2.092], P = 0.069) or esophageal and gastric cancer (fully adjusted HR 1.139, 95% CI [0.776-1.670], P = 0.506). Subgroup analyses showed that individuals who were younger (<65 years), male, and those without diabetes experienced a predominantly higher risk of developing digestive cancers. Similar results were observed when using CV, VIM, and ARV.ConclusionsFPG variability was significantly associated with increasing risk of digestive cancers, especially for pancreatic and colorectal cancer. Our study suggested a potential role of FPG variability in risk stratification of digestive cancers. Approaches that reduce FPG variability may lower the risks of incident digestive cancers among the general population. This trial is registered with ChiCTR-TNRC-11001489.

Dataset Information

Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population.

Publications

Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population.

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