Meta-Analysis of the Relationship between Common Type 2 Diabetes Risk Gene Variants with Gestational Diabetes Mellitus

<div><h3>Background</h3><p>A number of case-control studies were conducted to investigate the association of common type 2 diabetes (T2D) risk gene polymorphisms with gestational diabetes mellitus (GDM). However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between these polymorphisms and GDM, hence achieve a better understanding to the relationship between T2D and GDM.</p> <h3>Methods</h3><p>PubMed, EMBASE, ISI web of science and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between 9 polymorphisms from 8 genes and susceptibility to GDM. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity among articles and their publication bias were also tested.</p> <h3>Results</h3><p>We identified 22 eligible studies including a total of 10,336 GDM cases and 17,445 controls. We found 8 genetic polymorphisms were significantly associated with GDM in a random-effects meta-analysis. These polymorphisms were in or near the following genes: TCF7L2 (rs7903146), MTNR1B (rs10830963), IGF2BP2 (rs4402960), KCNJ11 (rs5219), CDKAL1 (rs7754840), KCNQ1 (rs2237892 and rs2237895) and GCK (rs4607517); while no association was found for PPARG with GDM risk. Similar results were also observed under dominant genetic model for these polymorphisms.</p> <h3>Conclusions</h3><p>This meta-analysis found 8 genetic variants associated with GDM. The relative contribution and relevance of the identified genes in the pathogenesis of GDM should be the focus of future studies.</p> </div

Supplementary document for Scintillation Minimization versus Intensity Maximization in Optimal Beams - 6478735.pdf

Supplementary material

The flow chart of the included studies.

<p>The flow chart of the included studies.</p

Characteristics of the studies included in the meta-analysis.

<p>OGTT: Oral Glucose Tolerance Test, IGDW: International Gestational Diabetes Workshop, ADA: American Diabetes Association, NA: Not Available.</p

Results of the pooled data analyses for the 9 studied polymorphisms and gestational diabetes mellitus risk.

<p>Results of the pooled data analyses for the 9 studied polymorphisms and gestational diabetes mellitus risk.</p

Cephalometric tracing and major measurements.

<p>Co-Gn (mm), mandibular unit lengh; Go-Gn (mm), mandibular corpus lengh; SN (mm) anteroposterior lengh of cranial base; wits (mm), length of distance AO-BO; ANB, anteroposterior relation of maxilla and mandible; SNA, anteroposterior maxillary position to anterior cranial plane; SNB, anteroposterior mandibular postion to anterior cranial plane; SN to GoGn (angle1), inclination of SN to mandibular plane GoGn; SN to FH (angle 2), inclination of SN to FH plane; FH to GoGn (angle 3), inclination of FH to mandibular plane GoGn.</p

The pedigree chart of mandibular prognathism families.

<p>The mandibular prognathism samples are indicated by darkened (affected) circles or squares. The squares indicate male; the circles indicate female; the diagonal lines indicate deceased family members.</p

The cephalometric variables that differ between affected and unaffected individuals.

<p>Footnotes:</p><p>*, cephalometric standards of China.</p><p>ANB, anteroposterior relationship of the maxilla and mandible.</p><p>SNA, anteroposterior maxillary position to anterior cranial plane.</p><p>SNB, anteroposterior mandibular position to anterior cranial plane.</p><p>Wits (mm), length of AO-BO distance.</p><p>ANS-Ptm (mm), maxillary unit length.</p><p>Co-Po (mm), mandibular unit length.</p

Chart of LOD and NPL value on 4p16.1.

<p>X axis indicates position from p terminus of chromosome (cM). Dashed line indicates LOD scores, and solid line indicates NPL scores. LOD: logarithm (base 10) of odds. NPL: value of non-parametric linkage analysis.</p

Fluorescence Quenching Studies of Potential-Dependent DNA Reorientation Dynamics at Glassy Carbon Electrode Surfaces

The potential-dependent reorientation dynamics of double-stranded DNA (ds-DNA) attached to planar glassy carbon electrode (GCE) surfaces were investigated. The orientation state of surface-bound ds-DNA was followed by monitoring the fluorescence from a 6-carboxyfluorescein (FAM6) fluorophore covalently linked to the distal end of the DNA. Positive potentials (i.e., +0.2 V vs open circuit potential, OCP) caused the ds-DNA to align parallel to the electrode surface, resulting in strong dipole–electrode quenching of FAM6 fluorescence. Switching of the GCE potential to negative values (i.e., −0.2 V vs OCP) caused the ds-DNA to reorient perpendicular to the electrode surface, with a concomitant increase in FAM6 fluorescence. In addition to the very fast (submilliseconds) dynamics of the initial reorientation process, slow (0.1–0.9 s) relaxation of FAM6 fluorescence to intermediate levels was also observed after potential switching. These dynamics have not been previously described in the literature. They are too slow to be explained by double layer charging, and chronoamperometry data showed no evidence of such effects. Both the amplitude and rate of the dynamics were found to depend upon buffer concentration, and ds-DNA length, demonstrating a dependence on the double layer field. The dynamics are concluded to arise from previously undetected complexities in the mechanism of potential-dependent ds-DNA reorientation. The possible origins of these dynamics are discussed. A better understanding of these dynamics will lead to improved models for potential-dependent ds-DNA reorientation at electrode surfaces and will facilitate the development of advanced electrochemical devices for detection of target DNAs