Tumor Necrosis Factor-α Gene -308 G/A Polymorphism Modulates the Relationship between Dietary Fat Intake, Serum Lipids, and Obesity Risk in Black South African Women

Abstract

The prevalence of obesity and related disease risk is high in black South African (SA) women, possibly influenced by the dietary transition associated with urbanization. This study explored interactions between dietary fat intake and the tumor necrosis factor-alpha (TNFA) -308 G/A polymorphism on obesity, insulin resistance, and serum lipid concentrations in urbanized black SA women. Normal-weight (n = 105) and obese (n = 118) women underwent measurements of body composition, fat distribution, fasting serum lipids, glucose and insulin concentrations, and dietary intake. Participants were genotyped for the functional TNFA -308 G/A polymorphism. The genotype or allele frequency of the TNFA -308 G/A polymorphism did not differ between the BMI groups. However, when dietary fat intake was 30% of total energy intake [percentage energy (%E)], the odds of being obese with the TNFA GA+AA genotype was only 12% of that with GG, but increasing intake of dietary fat (%E) was associated with a significantly faster rate of increase in obesity risk in women with the TNFA GA+AA genotype compared with those with the GG genotype (P = 0.036). There were significant diet-gene interactions between alpha-linolenic acid (%E) and the total cholesterol:HDL-cholesterol ratio (P = 0.036), and PUFA (%E) and LDL cholesterol levels (P = 0.026), with participants with the A allele being more responsive to changes in relative fat intake. The TNFA -308 G/A polymorphism modified the relationship between dietary fat intake, obesity risk, and serum lipid concentrations in black SA women.

The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

“…The methods used in this study have been described in detail previously. 1 In brief, basic anthropometric measurements, including weight, height and waist and hip circumferences were taken, and whole body composition was measured using dual-energy X-ray absorptiometry (Hologic Discovery-W, software version 12.1, Hologic Inc., Bedford, MA, USA). Abdominal visceral and subcutaneous adipose tissue areas were measured using computerized tomography (Toshiba Xpress Helical Scanner, Toshiba, Tokyo, Japan) at the level of L4-L5 lumbar vertebrae.…”

“…Studies from our laboratory, 1 and others [1][2][3] have shown that dietary fat intake modifies the relationship between the tumor necrosis factor-a gene (TNFA) -308 G4A polymorphism (rs1800629) and adiposity, and serum lipid concentrations. Common to all these studies was that the pro-inflammatory A allele of the functional TNFA-308 G4A polymorphism was associated with increased risk for obesity and dyslipidemia, and appeared to be more responsive to dietary fat intake.…”

“…1,4 Differences in these relationships may be explained, in part, by ethnic differences in the distribution of inflammatory gene polymorphisms and inflammatory gene expression, 5,6 insulin sensitivity, 6 obesity risk, dietary fat and specific fatty acid intake, and serum lipid concentrations between black and white SA women. 1,7 The functional -308 G4A polymorphism within the promoter region of the TNFA gene is in close proximity to the TNFA -238 G4A polymorphism (rs361525).…”

“…1,4 Differences in these relationships may be explained, in part, by ethnic differences in the distribution of inflammatory gene polymorphisms and inflammatory gene expression, 5,6 insulin sensitivity, 6 obesity risk, dietary fat and specific fatty acid intake, and serum lipid concentrations between black and white SA women. 1,7 The functional -308 G4A polymorphism within the promoter region of the TNFA gene is in close proximity to the TNFA -238 G4A polymorphism (rs361525). Although a number of studies have investigated the TNFA -308 G4A polymorphism, only a few have reported on the TNFA -238 G4A polymorphism and obesity, 8,9 and to our knowledge only one study has investigated the interaction between dietary fat intake and this polymorphism on adiposity and serum lipid concentrations.…”

“…1,4 Inclusion criteria included: no previous diagnosis or undergoing therapy for diabetes, hypertension, dyslipidemia, HIV or other metabolic diseases, and not currently pregnant or lactating. Only women were included because of the high prevalence of overweight and obesity seen in both black and white SA women, and because of the differences in serum lipids between black and white women, which was previously described.…”