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Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children.

ABSTRACT: BACKGROUND:The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility. METHODS:The genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays. RESULTS:Statistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C?>?T, rs10735810 and TaqI, C?>?T, rs731236) between T1DM patients and controls (P??T, rs7975232) and BsmI (A?>?G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and?>?6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes. CONCLUSIONS:Our results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.

SUBMITTER: Rasoul MA

PROVIDER: S-EPMC6404350 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children.

Rasoul Majedah A MA Haider Mohammad Z MZ Al-Mahdi Maria M Al-Kandari Hessa H Dhaunsi Gursev S GS

BMC pediatrics 20190307 1

<h4>Background</h4>The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility.<h4>Methods</h4>The genotypes of four VDR gene polymorph ...[more]

PMID: 30845908

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Project description:PurposeThe purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.MethodsThirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose < 11.1 mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.ResultsG__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.ConclusionsG__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.

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Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children.

Publications

Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children.

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