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Association analysis of polymorphisms at the interleukin-1 locus in essential hypertension
1Basic & Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, The University of Sydney, Sydney, New South Wales, Australia.
Insights
Genetic variations in the interleukin-1 gene cluster were studied for their link to hypertension. While IL1B gene polymorphisms showed no association, minor alleles of the IL1RN gene were more frequent in hypertension patients.
Area of Science:
- Genetics
- Immunology
- Cardiovascular Disease
Background:
- Infections like H. pylori and C. pneumoniae are linked to cardiovascular disease (CAD) and hypertension (HT).
- Pro-inflammatory cytokines released during infection can cause vascular damage.
- Genetic variations in cytokine genes may influence hypertension development.
Purpose of the Study:
- To investigate the association between polymorphisms in the interleukin-1 (IL1) gene cluster and hypertension.
- To examine the IL1B C(-31)T polymorphism and the IL1RN gene's tandem repeat variant for their potential role in HT.
Main Methods:
- Genotyping of IL1B C(-31)T and IL1RN polymorphisms in white Anglo-Celtic individuals from Sydney, Australia.
- Comparison of genotype and allele frequencies between normotensive (NT) and hypertensive (HT) cohorts.
- Statistical analysis using chi-squared tests to determine associations.
Main Results:
- No significant association was found between the IL1B C(-31)T polymorphism and hypertension (P = 0.55).
- The frequency of the T allele in IL1B was similar in both normotensive and hypertensive groups (0.30 vs. 0.31).
- A significant increase in the combined frequency of minor alleles (IL1RN*3, *4, *5) of the IL1RN gene was observed in the hypertensive cohort (P = 0.004).
Conclusions:
- The IL1B C(-31)T polymorphism is not associated with hypertension in the studied population.
- Increased frequency of minor alleles of the IL1RN polymorphism suggests a potential genetic susceptibility to hypertension.
- Further research is warranted to elucidate the role of IL1RN variants in the pathogenesis of hypertension.
Abstract:
Infection with microorganisms such as Helicobacter pylori and Chlamydia pneumoniae has been associated with coronary heart disease (CAD) and hypertension (HT). Infection increases the release of pro-inflammatory cytokines, thus facilitating interactions that lead to vascular damage and other effects. We hypothesized that genetically determined differences in activity or responsiveness of cytokine(s) might contribute to HT. The interleukin-1 gene (IL1) cluster on chromosome 2q14 contains three related genes (IL1A, IL1B, and IL1RN) located within a 430-kb region. These encode IL-1alpha and IL-1beta, as well as their endogenous receptor antagonist, IL-1ra. The IL1RN gene has a penta-allelic 86-bp tandem repeat in intron 2. Allele IL1RN* 2 is associated with a wide range of chronic inflammatory and autoimmune conditions, and its combination with the -31T variant of an IL1B C(-31)T polymorphism constitutes a pro-inflammatory haplotype that leads to vigorous IL-1beta production. We therefore tested each of these polymorphisms for association with HT. Subjects were white Anglo-Celtic residents of Sydney, Australia. Frequencies of IL1B C(-31)T genotypes CC, CT, and TT were 0.50, 0.40, and 0.10 in normotensive (NT) and 0.46, 0.46, and 0.08 in HT, respectively (chi(2) = 1.2, P = 0.55). T allele frequency in NT (0.30) was similar to that in HT (0.31). For the IL1RN variant, frequencies of alleles IL1RN* 1 and * 2 and combined minor alleles * 3, * 4, and * 5 were 0.61, 0.36, and 0.03 in NT and 0.54, 0.36, and 0.10 in HT, respectively (chi(2) = 11, P = 0.004). In conclusion, no association of the IL1B C(- 31)T with HT was found, whereas combined frequency of the minor alleles of the IL1RN polymorphism was increased in the HT cohort studied.