The association between genotype and BMI, health and lifestyle indicators as well as weight loss outcomes in overweight/obese Caucasian adults

Harbron, Janetta (Stellenbosch : University of Stellenbosch, 2011-03)

Thesis (PhD (Physiological Sciences))--University of Stellenbosch, 2011.

Includes bibliography.

Thesis

ENGLISH ABSTRACT: Genetic screening to improve obesity treatment outcomes is available despite the lack of conclusive evidence, specifically for Caucasian South Africans, in this regard. The aim of this study was to investigate the association between genotype (seven polymorphisms) and body mass index (BMI), health and lifestyle indicators in a cross-sectional sample of overweight/obese Caucasian adults (n=133), as well as the association between genotype and weight loss outcomes following an intervention (n=88) using a quasi experimental study design (time-series). The intervention consisted of a 24-week conservative weight loss programme that included dietary, physical activity and behavioural components. The primary null hypothesis for the cross-sectional sample, namely that there is no association between genotype and BMI, has not been rejected. A number of the secondary/exploratory hypotheses were rejected of which the most plausible associations (based on support by the literature and a physiological basis for the findng) are: 1) the mutant TT homozygotes of the GNB3 C825T polymorphism may have a higher risk to develop the metabolic syndrome (MetS) as they had significantly higher fasting triglyceride and glucose levels, a higher number of traits that met the diagnostic cut-off criteria for MetS and higher number of these subjects was diagnosed with MetS compared to the wild-type C-allele carriers; and 2) subjects with mutant alleles of either the FTO rs1421085 or rs17817449 polymorphisms may have poorer eating behaviours (a higher rigid control, habitual and emotional disinhibition, perceived hunger and internal locus for hunger) and higher intake of high-fat foods. The primary null hypothesis for the intervention sample, namely that there is no association between genotype and weight loss outcome, was not rejected for the FABP2 Ala54Thr, INSIG2 rs7566605, FTO rs1421085, ADRB3 Trp64Arg and GNB3 C825T polymorphisms. However, it was rejected in some instances indicating the following associations: 1) The wild-type TT homozygotes of the FTO rs17817449 polymorphism lost significantly more weight during the first two months of the program compared to the mutant allele carriers (this is a novel finding); 2) The wild-type Arg16Arg homozygotes of the ADRB2 Arg16Gly polymorphism lost significantly more weight during the first month of the program compared to the mutant allele carriers (this finding is supported by one other intervention study); 3) Subjects with a mutant C-allele of the INSIG2 rs7566605 polymorphism and a mutant Gly16-allele of the ADRB2 Arg16Gly polymorphism lost significantly less weight over the six month intervention period (this is a novel genegene interaction finding). A number of secondary/exploratory hypotheses were rejected, of which the most plausible finding include that the improvement in emotional disinhibition in the wild-type TT subjects of the FTO rs1421085 polymorphism was associated with a more pronounced decrease in BMI over the six month weight loss period. The integration of the results from this study with the literature indicates that there is insufficient evidence at this stage for genetic screening of the polymorphisms investigated in this study and the provision of evidence-based personalized recommendations for weight loss in obese individuals. It is recommended that these associations should be viewed as priority in future research.

AFRIKAANSE OPSOMMING: Genetiese sifting om die resultate van vetsug behandeling te verbeter is beskikbaar ten spyte van ‘n tekort aan genoegsame bewyse, spesifiek ten opsigte van Kaukasiërs van Suid-Afrika. Die doel van hierdie studie was om die assosiasie tussen genotipe (sewe polimorfismes) en liggaamsmassa indeks (LMI), gesondheid en lewenstyl indikatore in ‘n dwarssnit (cross-sectional) steekproef van oorgewig/vetsugtige Kaukasiër volwassenes (n=133) te ondersoek, asook die assosiasie tussen genotipe en gewigsverlies uitkomste na afloop van ‘n intervensie (n=88) in ‘n kwasi-eksperimentele studie ontwerp (tydreeks). Die intervensie het bestaan uit ‘n 24-week konserwatiewe gewigsverlies program met dieet, fisieke aktiwiteit en gedragskomponente. Die primêre nul hipotese vir die dwarsnit steekproef, naamlik dat daar geen assosiasie tussen genotipe en LMI is nie, is nie verwerp nie. ‘n Aantal sekondêre/spekulatiewe hipotesis is verwerp waarvan die mees geloofwaardige assosiasies (gebasseer op ondersteuning van die literatuur en ‘n fisiologiese basis vir die bevinding) die volgende insluit: 1) die mutante TT homosigote van die GNB3 C825T polimorfisme het moontlik ‘n hoër risiko vir die ontwikkeling van die metaboliese sindroom (MetS) aangesien hulle betekenisvolle hoër vastende trigliseriede en glukose vlakke gehad het, ‘n grooter aantal kenmerke gehad het wat aan die diagnostiese afsnykriteria vir MetS voldoen en ‘n grooter aantal van hierdie persone was met MetS gediagnoseer in vergelyking met die wilde-tipe C-alleel draers; en 2) persone met die mutante allele van die FTO rs1421085 of rs17817449 polimorfismes het moontlik ‘n swakker eetgedrag (‘n hoër rigiede kontrole, gewoonte en emosionele disinhibisie, waarneembare honger en interne lokus van honger) en ‘n hoër inname van hoë-vet voedsel. Die primêre nul hipotese vir die intervensie steekproef, naamlik dat daar geen assosiasie tussen genotipe en gewigsverlies uitkomste is nie, is nie vir die FABP2 Ala54Thr, INSIG2 rs7566605, FTO rs1421085, ADRB3 Trp64Arg en GNB3 C825T polimorfismes verwerp nie. Dit was egter in sommige gevalle vir die volgende assosiasies verwerp: 1) Die wilde-tipe TT homosigote van die FTO rs17817449 polimorfisme het betekenisvol meer gewig in die eerste twee maande van die program verloor in vergelyking met die mutante alleel draers (dit is ‘n nuwe bevinding); 2) Die wilde-tipe Arg16Arg homosigote van die ADRB2 Arg16Gly polimorfisme het betekenisvol meer gewig gedurende die eerste maand van die program verloor in vergelyking met die mutante alleel draers (hierdie bevinding word ondersteun deur een ander intervensie studie); 3) Persone met ‘n mutante C-alleel van die INSIG2 rs7566605 polimorfisme en ‘n mutante Gly16-allele van die ADRB2 Arg16Gly polimorfisme het minder gewig tydens die ses maande intervensie periode verloor (dit is ‘n nuwe geen-geen interaksie bevinding). ‘n Aantal sekondêre/ spekulatiewe hipoteses is verwerp, waarvan die mees geloofwaardigste bevinding insluit dat ‘n verbetering in emosionele disinhibisie van die wild-tipe TT persone van die FTO rs1421085 polimorfisme geassosieer was met ‘n meer prominente daling in LMI oor die ses maande gewigsverlies periode. Die integrasie van die resultate van hierdie navorsing met die literatuur dui aan dat daar op hierdie stadium onvoldoende bewyse vir genetiese sifting en die voorsiening van bewys-gebasseerde persoonlike aanbevelings vir gewigsverlies in vetsugtig individue bestaan vir die polimorfismes wat ondersoek is. Dit word aanbeveel dat hierdie assosiasies as prioriteit in toekomstige navorsing beskou moet word.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/6478
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