MTNR1B gene polymorphisms and susceptibility to Type 2 Diabetes: A pilot study in South Indians

Salman, Mohammed; Dasgupta, Shruti; Cholendra, A.; Venugopal, Pulamaghatta N.; Lakshmi, Gumpeny; Xaviour, D.; Rao, Jayashankar; D'Souza, Cletus J. M.

doi:10.1016/j.gene.2015.04.064

Cited by 23 publications

(9 citation statements)

References 26 publications

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“…Some studies examined the association of genetic polymorphism between GDM and T2D and supported the hypothesis that both had common genetic background 18 29 39 . In our study, only MTNR1B 40 and TCF7L2 41 involved in impaired insulin secretion, and IRS1 42 involved in insulin resistance in T2D were significantly associated with GDM. It further supports impaired insulin secretion and insulin resistance may involve in the pathogenesis of GDM as in T2D.…”

Section: Discussionmentioning

confidence: 46%

Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Cui

Tam

et al. 2016

Sci Rep

111

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Previous studies have demonstrated that gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2D) share common genetic polymorphisms. We conducted meta-analysis and subgroup analysis of all available variants and determined the effects of confounding and experimental components on the genetic association of GDM. Any case-controlled or cohort studies with genotype distribution compared GDM cases with controls were included. In total, 28 articles including 8,204 cases and 15,221 controls for 6 polymorphisms were studied. rs10830963(MTNR1B), rs7903146(TCF7L2), and rs1801278(IRS1) were significantly associated with the increased GDM risk. The association of rs4402960(IGF2BP2) and rs1800629(TNF-α) was significant only when the studies with control allele frequency deviation and publication bias were excluded. Further subgroup analysis showed the risk alleles of rs7903146(TCF7L2) and rs1801282(PPARG) were significantly associated with the GDM risk only in Asian, but not in Caucasian population. The OGTT test using 100 g, but not 75 g; and genotype detection by other assays, but not Taqman method, were also significantly associated with increased GDM risk in rs1801278(IRS1) and rs7903146(TCF7L2). Overall GDM was associated with rs10830963(MTNR1B), rs7903146(TCF7L2), and rs1801278(IRS1), but only rs7903146(TCF7L2) and rs1801282(PPARG) were significant in Asian populations. While rs1801278(IRS1) and rs7903146(TCF7L2) were significantly affected by OGTT protocol and genotyping methods.

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Section: Discussionmentioning

confidence: 46%

Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Cui

Tam

et al. 2016

Sci Rep

111

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“…Sometimes, the phenotype altering or diseases occurring was not associated with one single SNP changing but related to several SNPs. Global patterns of DNA sequence variation (haplotypes) defined by common SNPs have important implications for identifying disease and traits [ 36 , 37 ]. A previous study showed that the ALX1 haplotype has contributed to diversification of beak shapes among the Darwin’s finches and, thereby, to an expanded utilization of food resources [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Study on LOC426217 as a candidate gene for beak deformity in chicken

Bai¹,

Sun²,

Zhu³

et al. 2016

BMC Genet

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BackgroundThe beak deformity (crossed beaks) was found in some indigenous chickens of China, such as Beijing-You (BJY), Qingyuan Partridge, and Huxu Chickens. Birds with deformed beaks have reduced feed intake and drinking, impeded growth rate, and poor production performance. Beak deformity reduces the economy of poultry industry and affects animal welfare as well. The genetic basis of this malformation remains incompletely understood. LOC426217, also named claw keratin-like, was the most up-regulated gene in the deformed beaks from a previous digital gene expression (DGE) analysis and was selected as an important candidate gene for further analysis.ResultsIn the present study, quantitative real-time PCR (qRT-PCR) was firstly performed to determine the expression pattern of LOC426217 gene in deformed and normal beaks to verify the DGE results. Tissue-specific expression profile of this gene in 14 tissues was also determined using qRT-PCR. The LOC426217 was amplified from the genomic DNA of 171 deformed and 164 normal beaks, and sequenced to detect the single nucleotide polymorphisms (SNPs). The results showed that LOC426217 was significantly high-expressed in the deformed beaks, which was in good agreement with the DGE results. This gene was specifically high-expressed in beaks than other tissues. Eight SNPs were detected in LOC426217: -62G > T, 24 T > C, 36G > C, 192A > T, 204C > T, 222 T > C, 285G > T, and 363 T > C. Genotype frequency of G-62 T, T24C, G36C, T222C, and T363C loci was significant different between deformed and normal beaks. Haplotype analysis revealed one block with SNPs T24C and G36C, and one block with SNPs A192T, C204T, T222C, and G285T in normal birds, while the block with SNPs G36C and A192T in deformed ones.ConclusionsIt was concluded from these results that the over-expression of LOC426217 in the beak maybe related to the malformation. The polymorphisms of LOC426217 gene were associated with the beak deformity trait where the SNPs of G-62 T, T24C, G36C, T222C, and T363C loci maybe used as markers. The specific haplotype block in deformed birds may be a potential linkage marker for this trait.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0353-x) contains supplementary material, which is available to authorized users.

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“…Genotyping of the rs10830963 (C_3256858_10; Catalog number 4351379, Thermofisher Scientifics, USA) SNP was performed using TaqMan allelic discrimination assay, as previously described. 16,23 The annealing temperature was 62°C, and a genotyping success rate of 96% was achieved for rs10830963; sample quality issues were determined as major reasons for the failure in achieving 100% concordance for the genotyping of this polymorphism.…”

Section: Methodsmentioning

confidence: 99%

“…Of those genes that are consistently identified by different genetic screening approaches, melatonin receptor 1B ( MTNR1B ) (600804 OMIM) is associated with both GDM and type 2 diabetes. 12-16 MTNR1B maps to chromosome 11q21-q22 comprise 2 exons and 1 intron and encodes the MT2 protein, a 362-amino acid melatonin receptor. MTNR1B is strongly expressed in the brain, retina, and β-cells, and MT2 regulates blood glucose homeostasis through the regulation of insulin release via the melatonin signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center

et al. 2019

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BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease in pregnancy that causes carbohydrate intolerance and hyper-glycemia. Genome-wide association studies and meta-analyses have found that the single nucleotide polymorphisms (SNPs) rs1387153 and rs10830963 of the melatonin receptor 1B (MTNR1B) gene are associated with GDM. No studies on the MTNR1B gene effect on GDM have been performed in Saudis, other Arabs, or other Middle Eastern populations.OBJECTIVES: Investigate the association of genotype or allele frequencies of the two SNPs with GDM and with clinical parameters related to GDM.DESIGN: Case-control study.SETTINGS: Tertiary care center, Riyadh.PATIENTS AND METHODS: We recruited 400 pregnant Saudi women ages 18-45 years (200 were diagnosed with GDM, and 200 were healthy controls). Biochemical assays were performed, and rs1387153 and rs10830963 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis and real-time polymerase chain reaction with TaqMan genotyping.MAIN OUTCOME MEASURES: The association of MTNR1B gene (rs1387153 and rs10830963 polymorphisms) with GDM and with biochemical parameters related to GDM.SAMPLE SIZE: 200 GDM cases and 200 non-GDM controls.RESULTS: Differences in allele frequencies for GDM vs non-GMD were statistically significant or nearly significant for both SNPs after adjustment for age and body mass index. In a logistic regression analysis, genotype TT was positively associated with post-prandial blood glucose (P=.018), but other associations were not statistically significant.CONCLUSION: The odds ratios for the associations between the rs1387153 and rs10830963 SNPs and GDM exceeded 1.5-fold, which is higher than typically reported for diseases with complex genetic background. These effect sizes for GDM suggest pregnancy-specific factors related to the MTNR1B risk genotypes.LIMITATIONS: Only two SNPs were studied.CONFLICT OF INTEREST: None.

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MTNR1B gene polymorphisms and susceptibility to Type 2 Diabetes: A pilot study in South Indians

Cited by 23 publications

References 26 publications

Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Study on LOC426217 as a candidate gene for beak deformity in chicken

MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center

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