Association of interleukin-4 and interleukin-17F polymorphisms in periodontitis in Dravidian ethnicity.

BACKGROUND: Complex network of pro and anti-inflammatory cytokines are known to act in inflamed periodontal tissue. This study explores the distribution of interleukin (IL)-4 (+33 C/T) and IL-17F (7383A/G, 7488A/G) gene polymorphism in chronic and aggressive periodontitis subjects of Dravidian ethnicity. MATERIALS AND METHODS: This case control study consisted of 124 periodontitis individuals comprising of 63 chronic and 61 aggressive periodontitis subjects as cases, and control group consisted of 101 healthy subjects. All subjects were genotyped for IL-4 + 33C/T, IL-17F 7383A/G, 7488A/G by polymerase chain reaction amplification followed by TaqMan assay for IL-4 + 33C/T, restriction enzyme digestion and gel electrophoresis for IL-17F 7383A/G and sequencing for IL-17F 7488A/G. RESULTS: IL-4 + 33C/T was significantly associated with periodontitis (P < 0.05) at both allelic and genotypic level. In subgroup analysis also significant difference (P < 0.05) in allelic distribution between aggressive periodontitis and control group for loci IL-4 + 33C/T was noted. However, there was a lack of association between IL-17F 7383A/G and IL-17F 7488A/G with periodontitis and its sub-groups at both allelic and genotypic levels. CONCLUSIONS: In Malayalam speaking Dravidian population IL-4 + 33C/T loci appears to be an important risk factor for periodontal disease with a leaning towards aggressive periodontitis. The association between IL-17F at 7383A/G and 7488A/G loci with either chronic or an aggressive periodontitis could not be ascertained.

Corpora amylacea deposition in the hippocampus of patients with mesial temporal lobe epilepsy: A new role for an old gene.

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is the most common medically refractory epilepsy syndrome in adults, and hippocampal sclerosis (HS) is the most frequently encountered lesion in patients with MTLE. Premature accumulation of corpora amylacea (CoA), which plays an important role in the sequestration of toxic cellular metabolites, is found in the hippocampus of 50–60% of the patients who undergo surgery for medically refractory MTLE-HS. However, the etiopathogenesis and clinical importance of this phenomenon are still uncertain. The ABCB1 gene product P-glycoprotein (P-gp) plays a prominent role as an antiapoptotic factor in addition to its efflux transporter function. ABCB1 polymorphism has been found to be associated with downregulation of P-gp expression. We hypothesized that a similar polymorphism will be found in patients with CoA deposition, as the polymorphism predisposes the hippocampal neuronal and glial cells to seizure-induced excitotoxic damage and CoA formation ensues as a buffer response. MATERIALS AND METHODS: We compared five single nucleotide polymorphisms in the ABCB1 gene Ex06+139C/T (rs1202168), Ex 12 C1236T (rs1128503), Ex 17-76T/A (rs1922242), Ex 21 G2677T/A (rs2032582), Ex26 C3435T (rs1045642) among 46 MTLE-HS patients of south Indian ancestry with and without CoA accumulation. RESULTS: We found that subjects carrying the Ex-76T/A polymorphism (TA genotype) had a five-times higher risk of developing CoA accumulation than subjects without this genotype (Odds ratio 5.0, 95% confidence intervals 1.34-18.55; P = 0.016). CONCLUSION: We speculate that rs1922242 polymorphism results in the downregulation of P-gp function, which predisposes the hippocampal cells to seizure-induced apoptosis, and CoA gets accumulated as a buffer response.

Drug resistance in epilepsy and the ABCB1 gene: The clinical perspective.

Multidrug resistance is one of the most serious problems in the treatment of epilepsy that is likely to have a complex genetic and acquired basis. Various experimental data support the hypothesis that over-expression of antiepileptic drug (AED) transporters may play a pivotal role in drug resistance. Hyyt 6however, key questions concerning their functionality remain unanswered. The idea that P-glycoprotein, encoded by the ABCB1 gene, might mediate at least part of the drug resistance was met with both enthusiasm and skepticism. As in oncology, initial optimism has been clouded subsequently by conflicting results. The first study reporting a positive association between genetic variation in the P-glycoprotein and multidrug-resistant epilepsy was published in 2003. Since then, several other genetic association studies have attempted to verify this result. However, taken overall, the role of P-glycoprotein in drug resistance in epilepsy still remains uncertain. We intend to critically review the inherent problems associated with epilepsy pharmacogenetic studies in general and with ABCB1 polymorphisms studies in particular. The lessons learnt from the ABCB1 studies can help us to guide future association genetics studies to investigate AED resistance, and thereby taking us closer to the cherished dream of personalized AED therapy.