Association between G⁻³⁰⁸A polymorphism of the tumor necrosis factor‐α gene and 24‐hour ambulatory blood pressure values in type 1 diabetic adolescents

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine, which also influences blood pressure (BP). The G-308A polymorphism of the TNF-alpha gene is associated with altered TNF-alpha production. The prevalence of the TNF-alpha-308A allele is reportedly higher among patients with type 1 diabetes mellitus (T1DM) than in the healthy population. In this study we investigated whether this genetic polymorphism might correlate with BP values in diabetic adolescents. Ambulatory BP monitoring (ABPM) was performed in 126 adolescents with T1DM (mean age: 14 +/- 2.4 years). The TNF-alpha G-308A genotype was determined by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methodologies. ABPM results were related to healthy reference values and are given as standard deviation score (SDS). The prevalence of the -308A allele was higher in diabetic adolescents than the Hungarian reference population (0.26 vs 0.14, p < 0.01). TNF-alpha genotype was associated both with systolic and diastolic BP values (p < 0.01 and p < 0.01, respectively). In patients with TNF-alpha-308GG and -308GA/AA genotypes, the 24-h systolic BP average values were 0.37 +/- 1.33 and -0.38 +/- 1.28 SDS, while 24-h diastolic BP average values were 0.09 +/- 1.30 and -0.67 +/- 1.31 SDS. Hence, the TNF-alpha-308A allele carrier state appears to be associated with lower systolic and diastolic BP values.

Family-based analysis of tumor necrosis factor and lymphotoxin-α tag polymorphisms with type 1 diabetes in the population of South Croatia

“…A significant increase in TNF −308 allele A and G/A and A/A genotypes was found in North Indian T1DM cases [17,19]. Similarly, an increase in the prevalence of the TNF −308 A allele was reported in Hungarian diabetic patients [20]. Associations of the TNF/ LTA haplotypes and LTA +249A/G SNP with T1DM, was suggested to be independent of HLA in the Moroccan and Bahraini populations [18,22].…”

“…However, several other studies found an independent effect of TNF/LTA with T1DM [17][18][19][20]. TNF involvement in the destruction of pancreatic β-cells [10,11] and multiple inflammatory activities of TNF and LTA cytokines make them plausible targets for revealing molecular susceptibility to T1DM.…”

“…According to Makhatadze there is a localization of TNF and LTA genes within the HLA complex, as shown in Figure 1 [8]. Two TNF gene promoter single nucleotide polymorphisms (SNPs), G-238A (rs361525) and G-308A (rs1800629), have frequently been studied [6,[16][17][18][19][20][21][22]. However, inconsistencies in SNP designation through various LTA gene studies makes difficult to distinguish and differentiate investigated SNPs [6,7,18,22].…”

“…However, inconsistencies in SNP designation through various LTA gene studies makes difficult to distinguish and differentiate investigated SNPs [6,7,18,22]. Studies in North Indian, Hungarian, Bahraini, and Moroccan populations observed associations of TNF -308 SNP and TNF/LTA haplotypes with T1DM independently of HLA loci [17][18][19][20]22]. On the other hand, TNF/LTA T1DM associations in Chinese, Caucasian, and Polish populations were explained by dependence on HLA alleles [6,16,21].…”

Association of tumor necrosis factor‐α ‐308 G/A gene polymorphism with coronary artery diseases: An evidence‐based study

“…In particular, Kriskovszky and colleagues found that the TNF-α 308A was related with the low blood pressure in diabetic adolescents. 31 Another study showed that TNF-α 308G was associated with increased risk of hypertension. 32 Ito et al, 33 investigated the correlation of TNF-α with atherogenic risk factors in women.…”