ABCMdb

PMID: 25143473

Rolim AL, Lindsey SC, Kunii IS, Crispim F, Moises RC, Maciel RM, Dias-da-Silva MR
The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis.
J Mol Endocrinol. 2014 Oct;53(2):295-301. doi: 10.1530/JME-14-0083. Epub 2014 Aug 20., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC8 p.Ala1369Ser Additionally, the SUR1 Ala1369Ser variant appears to be associated with insulin sensitivity. Login to comment 3 ABCC8 p.Ala1369Ser We examined the ABCC8 gene at the single nucleotide level using PCR-restriction fragment length polymorphism (RFLP) analysis to determine its allelic variant frequency and calculated the frequency of the Ala1369Ser C-allele variant in a cohort of 36 Brazilian TPP patients in comparison with 32 controls presenting with thyrotoxicosis without paralysis (TWP). Login to comment 27 ABCC8 p.Ala1369Ser In this study, we explore the relationship between the ABCC8 gene variant Ala1369Ser and susceptibility to TPP. Login to comment 38 ABCC8 p.Ala1369Ser We searched for the ABCC8 gene variant Ala1369Ser (rs757110) using PCR-restriction fragment length polymorphism (PCR-RFLP) screening and subsequent direct sequencing analyses. Login to comment 39 ABCC8 p.Ala1369Ser The ABCC8 gene region encompassing the Ala1369Ser variant (rs757110) was amplified using the following primers: forward, 50 -GGG AAG AGT CCA AGG AGG AG-30 , and reverse, 50 -CAG GAG ACT GCG ATG TCT GA-30 . Login to comment 49 ABCC8 p.Ala1369Ser The association between the ABCC8 Ala1369Ser variant and the risk of TPP was estimated by the odds ratio (OR) and considering the 95% CIs, using the non-risk genotype (ACCAA) as a reference. Login to comment 59 ABCC8 p.Ala1369Ser The distribution of the Ala1369Ser (rs757110) genotype frequency was examined in TPP patients and TWP subjects; representative electropherogram sequences and restriction analyses are shown in Fig. 1. Login to comment 67 ABCC8 p.Ala1369Ser Discussion In this case-control study, we demonstrate for the first time, to our knowledge, that the frequency of the Ala1369 variant is significantly higher in TPP patients than in TWP patients, revealing an association between the insulin-sensitivity-related p.Ala1369Ser genetic variant of SUR1 and TPP. Login to comment 78 ABCC8 p.Ala1369Ser In this study, we screened exon 33-37, where most mutations causing hyperinsulinaemia exist and focused on the most important SUR1 variant that confers insulin sensitivity, which is largely known as the non-synonymous variant p.Ala1369Ser (Hamming et al. 2009, Villareal et al. 2009). Login to comment 79 ABCC8 p.Ala1369Ser ABCC8 p.Ala1369Ser Interestingly, the SUR1 p.Ala1369Ser variant appears to be in linkage disequilibrium (LD) with the p.Glu23Lys Figure 1 Sequencing and genotyping results of the p.Ala1369Ser variant (rs757110). Login to comment 86 ABCC8 p.Ala1369Ser (B) Representative electropherogram sequences of the SUR1 p.Ala1369Ser variant detected in patients corresponding to lanes 3, 5 and 7. Login to comment 92 ABCC8 p.Ala1369Ser These authors also demonstrated that the SUR1 p.Ala1369Ser variant may be responsible for T2D risk by decreasing the ATP sensitivity of the KATP channel (Hamming et al. 2009). Login to comment 105 ABCC8 p.Ala1369Ser Table 2 Genetic association analysis of the SUR1 p.Ala1369Ser variant observed in the TPP and control groups. Login to comment 106 ABCC8 p.Ala1369Ser The allele (C/A) and genotype (AA, CC, AC and CC or AC) for the p.Ala1369Ser (rs757110) in thyrotoxic periodic paralysis (TPP) patients, thyrotoxic without paralysis (TWP) control patients and the population genetics control (1000 Genomes Project/1KGP) are listed with frequencies, odds ratio (OR), CI of 95% and P value for comparisons when available. Login to comment