Associations of MHC genes with levels of caries-inducing organisms and caries severity in African-American women

Abstract

The aim of this investigation was to evaluate the relationship between MHC alleles at the HLA-DRB1, DQB1 and TNFa microsatellite loci and levels of oral bacteria that play a role in the etiology of dental caries, and the DMFS index in 186 AA primparous women. The average age of the cohort was 20.8 ± 3.7 years. The median DMFS index was 9 (range 0–68). High levels of S. mutans were positively associated with DRB1∗3 and DRB1∗4 presence (p ⩽ 0.005). DRB1∗8 was positively associated with higher levels of S. mutans as a percentage of total Streptococci (p = 0.04). DRB1∗1 was positively associated with high levels L. casei (p = 0.04). DQB1 alleles were not observed associated with oral bacterial levels. TNFa allele 103 was negatively associated (p = 0.04), and TNFa 117 was positively associated (p = 0.007), with high levels of L. acidophilus. No significant associations were observed between any DRB1, DQB1 or TNFa allele and the DMFS index. These results support an hypothesis of an association between host HLA class II and TNFa genetic profile and colonization of S. mutans, L. casei, and L. acidophilus thought to be pathogens involved in the etiology of dental caries.

Introduction

The first evidence that bacteria are involved in the etiology of caries was presented nearly 75 years ago [1]. Much later it was shown that Streptococcus mutans is one of the caries-associated bacteria and that the primary source of this microbe is one’s mother 2, 4. It is now accepted that a number of bacteria, including Lactobacillus acidophilus and Lactobacillus casei contribute to the cariogenic potential of dental plaque although the mutans streptococci are the most prevalent [2]. Although environmental factors such as diet and fluoride also clearly influence caries susceptibility 1, 2, 3, 4, 5, twin studies have shown that genetic factors contribute to caries susceptibility 5, 6.

If one accepts that caries susceptibility is in part influenced by the oral microbiota then one’s immune response capability may also be modulating this process. There are data to support an immunological basis for caries resistance. Caries-free individuals have been observed to have increased serum antibody titers to streptococcal antigens [7]. Moreover, the T lymphocytes from these individuals have an enhanced ability to proliferate upon exposure to streptococcal antigens [8]. Caries-resistant subjects have also been observed to generate greater T-helper cell activity to a lower dose of purified streptococcal antigen compared to caries-prone individuals [9].

There is some evidence that genes within the MHC may influence responsiveness to cariogenic bacterium. Investigators have observed a relationship between superficial caries and the aggregation of DR-positive cells in the dental pulp [10]. With deeper caries lesions the aggregation of DR-positive cells extended to the odontoblast layer. A higher dose of purified streptococcal antigen was required to stimulate release of T helper activity from cells that were HLA-DR4 compared to other HLA phenotypes [9]. In contrast a low-dose of antigen was required to stimulate release of T helper activity from cells carrying the HLA-DR 1, 2, 3, 6 cross reactive groups. In another study HLA-DR4 was not found in immunosuppressed renal transplant individuals who had low levels of mutans streptococci colony forming units (CFUs), but was present in 48% of those with high levels [11]. In healthy individuals there was an increase, although not significant, in the frequency of DR4 in those with high levels of mutans streptococci CFUs. Among a group of dental faculty, students and staff the frequency of DR4 was also increased in those with high levels of mutans streptococci CFUs [12]. However, this difference did not reach statistical significance.

Many of the aforementioned studies have been limited by relatively small sample size. Moreover, none of these studies have included African-Americans (AA). This group is of particular interest because they experience higher MS and caries rates and AA mothers have been reported to transmit MS to their infants with greater fidelity than white mothers [3]. We therefore designed a study to assess the relationship of genes within the major histocompatibility complex to oral bacterial levels and the DMFS index in a population of AA women. In addition to HLA-DRB1, DQB1 alleles, which are involved in presenting exogenous antigens to T cells, we also assessed TNFa microsatellite alleles. The TNFa microsatellite loci lies adjacent to TNF and has been implicated as part of extended haplotypes that determine susceptibility or resistance to disease and level of TNFα secretion 13, 14. Thus, we tested the hypothesis that the level of oral cariogenic bacteria and subsequent development of caries would in part be determined by polymorphisms at these loci.