Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Abstract

BackgroundCytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention.MethodsThis 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-α -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype.ResultsIn the entire sample (66.7% women; mean age 56.5 ± 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-α -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention.ConclusionThe TNFα -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.

Asociación del polimorfi smo TNF-alpha -308 G/A con los cambios metabólicos secundarios a una dieta hipocalórica rica en proteínas/baja en hidratos de carbono versus una dieta hipocalórica estándar

“…Only one study has been designed with a surgical intervention; a surgical study with bariatric procedure (21) has shown that this polymorphism is not related to biochemical outcomes after a massive weight loss with a biliopancreatic diversion procedure. All previously cited studies have been conducted in Caucasian subjects, and only one study has evaluated a dietary intervention in a different ethnicity (22). In this design, -308 G/A SNP predisposed a better response of glucose metabolism to a dietary intervention.…”

Association of the <i>ADIPOQ</i> T45G polymorphism with insulin resistance and blood glucose: A meta-analysis

“…However, this study only assessed the genetic influence on IR using HOMA-IR under a codominant model and not the genetic influence on blood glucose. Furthermore, other studies [13,16,19,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] regarding the association between the ADIPOQ T45G polymorphism and IR have been reported.…”

“…In the eligible studies, 12 studies were held in Europe [14, 16, 21, 24-26, 29, 31-34, 36], 11 in Asia [13, 15, 17-20, 22, 23, 27, 28, 30], and 1 in Brazil involved white and non-white subjects [35]. All subjects in 2 [28,31] and 3 [13,21,29] studies were male and female, respectively.…”

“…The remaining 19 studies consisted of both male and female subjects. In all 25 studies, 2 involved obese subjects [23,32], 3 involved T2D subjects [19,27,36], 7 involved non-diabetic and non-obese subjects [13,22,24,26,30,33,35], and 13 involved healthy subjects [14-18, 20, 21, 24, 25, 28, 29, 31, 34] (Table 1). Genotype distributions in all studies were in Hardy-Weinberg equilibrium, except in 1 study [36].…”

Interleukin 6 (IL-6)andIL-10Promoter Region Polymorphisms Are Associated with Risk of Lumbar Disc Herniation in a Northern Chinese Han Population

“…In this study, we found an association of IL-6 SNPs with an increased risk of developing lumbar disc herniation. Genetic variations in the IL-6 promoter region could result in aberrant IL-6 transcription and expression (Fishman et al, 1998), thereby affecting individual susceptibility to various diseases (Curti et al, 2012). For example, the IL-6-572C/G polymorphism leads to replacement of cytidine by guanosine in the IL-6 promoter (Kitamura et al, 2002;MullerSteinhardt et al, 2004;Hamid et al, 2005;Lei et al, 2005), affecting IL-6 transcription and, in turn, changing IL-6 expression (Terry et al, 2000).…”