Increased frequency of rare missense PPP1R3B variants among Danish patients with type 2 diabetes.
PLoS One
; 14(1): e0210114, 2019.
Article
en En
| MEDLINE
| ID: mdl-30629617
ABSTRACT
BACKGROUND:
PPP1R3B has been suggested as a candidate gene for monogenic forms of diabetes as well as type 2 diabetes (T2D) due to its association with glycaemic trait and its biological role in glycogen synthesis.OBJECTIVES:
To study if rare missense variants in PPP1R3B increase the risk of maturity onset diabetes of the young (MODY), T2D or affect measures of glucose metabolism.METHOD:
Targeted resequencing of PPP1R3B was performed in 8,710 samples; MODY patients with unknown etiology (n = 54), newly diagnosed patients with T2D (n = 2,930) and population-based control individuals (n = 5,726, of whom n = 4,569 had normal glucose tolerance). All population-based sampled individuals were examined using an oral glucose tolerance test.RESULTS:
Among n = 396 carriers, we identified twenty-three PPP1R3B missense mutations, none of which segregated with MODY. The burden of likely deleterious PPP1R3B variants was significantly increased with a total of 17 carriers among patients with T2D (0.58% (95% CI 0.36-0.93)) compared to 18 carriers among non-diabetic individuals (0.31% (95% CI 0.20-0.49)), resulting in an increased risk of T2D (OR (95% CI) = 2.57 (1.14-5.79), p = 0.02 (age and sex adjusted)). Furthermore, carriers with diabetes had less abdominal fat and a higher serum concentration of LDL-cholesterol compared to patients with T2D without rare missense PPP1R3B variants. In addition, non-diabetic carriers had a higher birth weight compared to non-carriers.CONCLUSION:
Rare missense PPP1R3B variants may predispose to T2D.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Predisposición Genética a la Enfermedad
/
Diabetes Mellitus Tipo 2
/
Proteína Fosfatasa 1
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Pakistán