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

[摘要] ENGLISH ABSTRACT: Genetic screening to improve obesity treatment outcomes is available despite the lack of conclusiveevidence, specifically for Caucasian South Africans, in this regard.The aim of this study was to investigate the association between genotype (seven polymorphisms) andbody mass index (BMI), health and lifestyle indicators in a cross-sectional sample of overweight/obeseCaucasian adults (n=133), as well as the association between genotype and weight loss outcomes followingan intervention (n=88) using a quasi experimental study design (time-series). The intervention consisted ofa 24-week conservative weight loss programme that included dietary, physical activity and behaviouralcomponents.The primary null hypothesis for the cross-sectional sample, namely that there is no association betweengenotype and BMI, has not been rejected. A number of the secondary/exploratory hypotheses wererejected of which the most plausible associations (based on support by the literature and a physiologicalbasis for the findng) are: 1) the mutant TT homozygotes of the GNB3 C825T polymorphism may have ahigher risk to develop the metabolic syndrome (MetS) as they had significantly higher fasting triglycerideand glucose levels, a higher number of traits that met the diagnostic cut-off criteria for MetS and highernumber 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 poorereating behaviours (a higher rigid control, habitual and emotional disinhibition, perceived hunger andinternal locus for hunger) and higher intake of high-fat foods.The primary null hypothesis for the intervention sample, namely that there is no association betweengenotype and weight loss outcome, was not rejected for the FABP2 Ala54Thr, INSIG2 rs7566605, FTOrs1421085, ADRB3 Trp64Arg and GNB3 C825T polymorphisms. However, it was rejected in some instancesindicating the following associations: 1) The wild-type TT homozygotes of the FTO rs17817449polymorphism lost significantly more weight during the first two months of the program compared to themutant allele carriers (this is a novel finding); 2) The wild-type Arg16Arg homozygotes of the ADRB2Arg16Gly polymorphism lost significantly more weight during the first month of the program compared tothe mutant allele carriers (this finding is supported by one other intervention study); 3) Subjects with amutant C-allele of the INSIG2 rs7566605 polymorphism and a mutant Gly16-allele of the ADRB2 Arg16Glypolymorphism lost significantly less weight over the six month intervention period (this is a novel genegeneinteraction finding). A number of secondary/exploratory hypotheses were rejected, of which themost 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 sixmonth weight loss period.The integration of the results from this study with the literature indicates that there is insufficient evidenceat this stage for genetic screening of the polymorphisms investigated in this study and the provision ofevidence-based personalized recommendations for weight loss in obese individuals. It is recommendedthat these associations should be viewed as priority in future research.

[发布机构] Stellenbosch University