Interactions of CRP-SNPs with selected contributing factors in determining CRP concentrations in black South Africans

Abstract

Introduction: Non-communicable diseases, especially cardiovascular diseases, are on the rise globally, with low- and middle-income countries, including South Africa, at the epicentre of the increase in these conditions. The inflammatory origin of these diseases is increasingly being reported; however, most of the conducted research is focused on white populations. C-reactive protein (CRP) is of particular interest, as elevated concentrations, which are commonly observed in black individuals, are indicative of future cardiovascular disease risk, and limited information is available for this particular group. Objectives: We investigated whether specific factors, identified from an initial literature review were associated with elevated CRP concentrations in black individuals (as compared to white individuals), and if these factors associated with CRP single nucleotide polymorphisms (SNPs) in a manner that could alter the CRP phenotype. These specific factors that were identified from a thorough review of the current literature included (i) factors pertaining to socio-economic status or SES, (ii) lower vitamin D status and (iii) anthropometric markers together with a metabolic determinant of CRP: interleukin-6 (IL-6). Methods: This investigation was embedded in the Prospective Urban and Rural Epidemiology (PURE) study, where 2 010 apparently healthy participants were included at baseline in 2005. Data were collected on factors pertaining to their SES, dietary intake and various anthropometric, biochemical and physiological markers. Twelve CRP SNPs, previously analysed, were included in this study to investigate possible gene−environmental effects. Results: Overall, women presented with higher CRP concentrations than men. Apart from attaining twelve or more years of formal education, none of the other SES factors resulted in individuals presenting with an altered CRP phenotype. We also reported for the first time that harbouring the variant allele at the rs3093068 locus was associated with an increased risk of developing elevated CRP in smokers compared with non-smokers. No vitamin D x CRP SNP interactions were observed, although women co-presenting with low levels of vitamin D and high CRP concentrations were more likely to have poorer cardiovascular outcomes. However, some CRP polymorphisms were associated with an increased risk of presenting with an altered CRP phenotype when also harbouring this co-phenotype. Both IL-6 and CRP concentrations were elevated in individuals with increasing body weight, and waist circumference (WC) was an important predictor of elevated CRP. CRP was determined to be elevated in certain genotypes, even when similar IL-6 concentrations were observed between these alleles, indicating that the genetic variation had a greater effect on the expression of the CRP protein. It was established that WC, as a marker of abdominal adiposity, contributed substantially towards the elevated CRP concentrations. Conclusion: Here we extended the literature by investigating non-biological and biological factors that we gleaned from the literature to be of importance when trying to shed light on the regulation of CRP concentrations. We ascertained that certain demographic characteristics − smoking, vitamin D and anthropometry − were all determinants of the CRP phenotype of black individuals. As certain of these determinants are modifiable, we recommend that healthcare providers reduce CRP by educating/treating patients to optimise their vitamin D status and manage their WC and thus possibly curb diseases contingent on inflammation. This study highlights the need for the development of population-specific preventative strategies to overcome the pandemic of cardiovascular disease.