leky-latky/ADIPOQ-gen/asociovane-choroby
ADIPOQ
- Koduje Adiponektin
Polymorfismy genu pro adiponektin
- Reakce na mononenasycené tuky
- Gen exprimovaný v tukové tkáni.
- Reguluje metabolismus tuků
- Citlivost na inzulin
- Vliv na jo-jo efekt
- Hladinu adiponektinu
- Inconsistently associated with adiponectin levels or diabetes [1]
Common Variants in the Adiponectin Gene (ADIPOQ) Associated With Plasma Adiponectin Levels, Type 2 Diabetes, and Diabetes-Related Quantitative Traits, The Framingham Offspring Study
- Participants in the Framingham Offspring Study (n = 2,543, 53% women)
- Glycemic phenotypes and incident diabetes over 28 years of follow-up
- adiponectin levels were quantified [1]
Adiponectin levels
- Rs17300539 (-11391G/A)(5' promoter region ); Pnominal [Pn] = 2.6 × 10-8; Pempiric [Pe] = 0.0005 [1] - často genotypizováno
- Minor A allele
- Associated with higher adiponectin levels in a meta-analysis of >2,000 individuals [1]
- Seemed to enhance the ADIPOQ promoter activity and increased transcriptional activity [1]
- Strongest signal associated with adiponectin levels [1]
- Each minor allele (MAF = 0.10) increases adiponectin levels by 1.63 µg/ml
- Each 1 µg/ml increase in adiponectin levels decreases diabetes risk incidence by 8.1% (24) [1]
- Had <10% power to detect the effect of rs17300539 on diabetes incidence [1]
- Rs266729 (-11377C/G) - často genotypyzováno - kontroverzní výsledky studií [1]
- Rs822387 (5' promoter region ); Pn = 3.8 × 10-5; Pe = 0.001) [1]
- Minor C allele associated with higher adiponectin levels, confirming the report of Heid et al. [1]
- Rs6773957 (A 3'-untranslated region 3'UTR) Pn = 4.4 × 10-4; Pe = 0.005 [1]
- Strongest signal in this region of ADIPOQ
- Other SNPs in the 3'UTR nominally associated with adiponectin levels [1]
- Rs6444175 [1]
- A allele associated with higher adiponectin levels [1]
- Rs1501299 (+276G/T) [1]
- Minor T allele was associated with higher adiponectin levels
- In vitro data has not supported a functional role for rs1501299 in adiponectin expression
- Might be a marker, through linkage disequilibrium, of a functional variant in the 3'UTR region [1]
Diabetes
- Rs17366743, Y111H - A nonsynonymous SNP - missense SNP of ADIPOQ - associated with [1]
- Diabetes incidence (HR 1.94 [95% CI 1.16–3.25] for the minor C allele; Pn = 0.01) [1]
- Higher mean fasting glucose over 28 years of follow-up (Pn = 0.0004; Pe = 0.004) [1]
- No other significant associations were found with other adiposity and metabolic phenotypes [1]
- Y›H change at codon 111 in exon 3 of ADIPOQ [1]
- Amino acid change from a Tyr (T allele) into a His (C allele) in position 111 of the adiponectin protein
- Hinge between the collagen and the globular domains of adiponectin
- Believed to disrupt the exonic splicing enhancer
- Could influence alternative splicing of the message
- Does not influence the level of the circulating adiponectin
- Could influence the functionality of the protein
- Decrease the insulin-sensitizing role of adiponectin
- Carrier individuals at higher risk of diabetes [1]
- The minor C allele in Framingham (3.6%)
- More frequent in HapMap CEU subjects (7.5%) [1]
- Diabetes survival and mean glucose were associated [1]
Life Test neznámého / neznámých polymorfismů ADIPOQ
Snad AA / AG ? - rs17300539 (-11391G/A) ???
- Alespoň jednou vzácnou kopií genu ADIPOQ pravděpodobně úspěšněji zabrání tzv. jojo efektu po snížení tělesné
- Asi 20 % lidí v populaci
Genotyp GG čeho ?
- Cca 80 % populace má běžný genotyp GG
- Musí věnovat zachování tělesné hmotnosti po zhubnutí větší úsilí
- Velmi pravděpodobné, že po zhubnutí se začne tělesná hmotnost opět zvyšovat
- Nejčastější chyba: snaha hubnout hladověním !
- Důležité jsou zdravé stravovací návyky - trvalé !!!
