Implication of the Pro12Ala polymorphism of the gene in type 2 diabetes and obesity in the French population-1

<p><b>Copyright information:</b></p><p>Taken from "Implication of the Pro12Ala polymorphism of the gene in type 2 diabetes and obesity in the French population"</p><p>BMC Medical Genetics 2005;6():11-11.</p><p>Published online 22 Mar 2005</p><p>PMCID:PMC1084346.</p><p>Copyright © 2005 Ghoussaini et al; licensee BioMed Central Ltd.</p>sity status, and Pro12Ala polymorphism were the explicative factors. A term of interaction BMI*Pro12Ala or obesity status*Pro12Ala was introduced. The Z score of BMI was used rather than BMI in analyses including obese children. (A) No evidence for interaction was found neither for Z score of BMI*Pro12Ala (p = 0.59) nor obesity status*Pro12Ala (p = 0.21) in 887 normal glucose tolerant lean and obese children (p = 0.58). (B) No evidence for interaction was found for BMI*Pro12Ala (p = 0.32) in 1372 normal glucose tolerant obese and lean adults subjects, but a borderline significant interaction was found for obesity status*Pro12Ala (p = 0.06)

Homology study showed that this amino acid was highly conserved through species for the c.1041C>A and c.1151C>T mutations.

<p>Homology study showed that this amino acid was highly conserved through species for the c.1041C>A and c.1151C>T mutations.</p

Clinical and hormonal data of patients with mutated <i>MAMLD1</i>.

<p>SD: standard deviation. ND: not determined. NA: not available. DHT: dihydrotestosterone. DHEA: dihydroepiandrsosterone. Parentheses indicate the standard deviation for height and weight and the normal range for hormone serum levels. Testes of 1–2 ml can be regarded as normal, as recently reported by Shibata et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Shibata1" target="_blank">[34]</a>.</p>*<p>It is notable that anti-mullerian hormone and inhibin were lowered in one case. <i>MAMLD1</i> is indeed reported to be expressed in Sertoli cells, as well <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Fukami1" target="_blank">[15]</a>.</p

Incidence of exonic polymorphisms p.P359S and p.N662S, and relative haplotypes in normal controls and 46,XY DSD patients.

<p>Controls are combined with the published series (matched for ethnicity of patients and controls) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Kalfa1" target="_blank">[13]</a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032505#pone.0032505-Chen1" target="_blank">[14]</a>. The χ-square test was performed. When combining all patients with the p.662G polymorphism whatever the p.359 allele, this p.662G was significantly more frequent in 46,XY DSD patients: 27.1% (n = 19) vs. 6.8% (n = 40), <i>p</i> = 0.0001.</p

Transactivation function of the variants of the MAMLD1 protein analyzed by the luciferase method.

<p>The activity is evaluated for pHes3-luc vector.</p

Electrochromatograms and pedigrees of the three patients with <i>MAMLD1</i> mutations.

<p>The black squares indicate patients with posterior hypospadias. All mutant sequences were controlled by wildtype (WT) DNA. Regarding case 1's family, only the members III-3 and II-4 were genotyped, as the other members in the pedigree declined genetic testing.</p

Tertiary structure prediction of the wildtype protein (left column) and with the mutants.

<p>3D structure was predicted at Protein Homology/analogY Recognition Engine (PhyreEngine) from the Structural Bioinformatics Group, Imperial College, London, at <a href="http:www.sbg.bio.ic.ac.uk/phyre~/" target="_blank">http:www.sbg.bio.ic.ac.uk/phyre~/</a>. The plain arrows show the changes in the shape of the protein between the wildtype and p.P384L.</p

Additional file 1: of Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

The questionnaire used in the current study. (PDF 620 kb