Assessment of chromosome 19 for genetic association in severe chronic periodontitis.

BACKGROUND: A genome-association study is a powerful tool for analyzing small gene effects in complex diseases such as chronic periodontitis (CP), although the cost of analysis is prohibitive. We designed a study using the DNA pooling method, which could be a breakthrough in lowering such costs. This study was conducted to assess the genetic association in severe CP in a Japanese population. METHODS: We adopted a DNA pooling method by genotyping 454 densely spaced microsatellite (MS) markers in chromosome 19 as a pilot study, with the possibility of future use in a whole-genome study. This can reduce the high cost and technical burden, which is generally unavoidable in a genomic association study. Pooled DNA samples from 300 case subjects, 300 control subjects, and 200 systemically healthy subjects were screened by genotyping MS markers. The case-control association in the candidate region was analyzed by individual typing of MS and single nucleotide polymorphisms (SNPs). RESULTS: The single MS marker allele 17 of 1902G31 was isolated in association with severe CP (P = 0.0012 for 2 x 2; P <0.046 for 2 x m, where m refers to the number of polymorphic alleles observed in a population). No other SNP or MS polymorphism hypothesized to affect biologic functions in the critical region was found in the linkage disequilibrium block analysis. CONCLUSIONS: We efficiently isolated the susceptible locus for severe CP in chromosome 19 and identified a useful marker to evaluate the risk for disease. This approach can be applied to a whole-genome study in severe CP.

Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians.

We performed a genome-wide association study with 23,465 microsatellite markers to identify genes related to adult height. Selective genotyping was applied to extremely tall and extremely short individuals from the Khalkh-Mongolian population. Two loci, 8q21.13 and 15q22.33, which showed the strongest association with microsatellites were subjected to further analyses of SNPs in 782 tall and 773 short individuals. The most significant association was observed with SNP rs2220456 at 8q21.13 (P = 0.000016). In the LD block at 15q22.32, SNP rs8038652 located in intron 1 of IQCH was strongly associated (P = 0.0003), especially the AA genotype of the SNP under a recessive model was strongly associated with adult height (P = 0.000046).

[The effects of intrathecally administered baclofen on somato-sympathetic reflex potentials].

We investigated the antinociceptive effect of intrathecally administered S(-)-baclofen and R (+)-baclofen in cats using somato-sympathetic reflex potentials derived from lumbar sympathetic ganglion by stimulation of the femoral nerve. S(-)-baclofen 10 mg maximally reduced both A reflex potential and C reflex potential to 65.3% and 83.7% of control values, respectively, 1 minute after the administration, but these changes were not significant. The inhibition of A reflex potential at this dosage was greater than that of blood pressure and heart rate induced by the same dosage of S(-)-baclofen. While, R(+)-baclofen 1 mg maximally inhibited A reflex potential to 48.6% of control value 20 minutes after the administration, and this change was significant (P < 0.05). The inhibition of A reflex potential was greater than that of blood pressure and heart rate induced by the same dosage of R(+)-baclofen. This dosage of baclofen reduced C reflex potential to 66.4% of control value 10 minutes after the administration. The degree of reduction of A and C reflex potentials induced by 1 mg of R(+)-baclofen was higher in comparison with that induced by 10 mg of S(-)-baclofen. These reduction of A and C reflex potentials were reversed by 1 to 1.5 mg of intrathecally administered saclofen. These results indicate that R(+)-baclofen has higher potency than S(-)-baclofen and suggest that S(-)-baclofen and R(+)-baclofen show antinociceptive effect by intrathecal administration. On the other hand, it is possible that these two drugs exert antinociceptive effect via A delta fiber.

[The effects of intrathecally administered neostigmine on somato-sympathetic reflex potentials].

BACKGROUND: Antinociceptive effect of intrathecal neostigmine has been investigated using withdrawal responses in laboratory experiments. However, neostigmine administered in this route can induce muscle weakness or sedation. As a result, these effect can modify withdrawal responses. In this study we investigated the antinociceptive effect of intrathecally administered neostigmine bromide (NB) in cats objectively and quantitatively using somato-sympathetic reflex potentials. METHODS: Anesthetized cats were inserted with a spinal catheter via atlanto-occipital membrane and 10 micrograms (n = 5), 50 micrograms (n = 5), 250 micrograms (n = 8) or 2 mg (n = 5) of NB was administered through this route. Somato-sympathetic reflex potentials (A and C reflex) derived from lumbar sympathetic ganglion by stimulation of the femoral nerve and mean arterial blood pressure (MAP) and heart rate (HR) in each dose were monitored and recorded. RESULTS: Reflex potential was reduced in a dose dependent fashion by NB but these changes were not significant. On the other hand, 250 micrograms and 2 mg of NB maximally reduced C reflex potential to 55.2% and 24.0% of control values respectively 20 minutes after the administration (P < 0.01), and this reduction was reversed by 250 to 2 mg of intrathecal administration of atropine sulfate to 89.4%, 68.6% of control values respectively. MAP and HR decreased in dose dependent fashion by NB to 57.6%, 65.2% of control values after the administration of 2 mg of NB and these cardiovascular changes recovered by intrathecally administered atropine sulfate. CONCLUSION: These results objectively indicate that intrathecally administered neostigmine bromide shows antinociceptive effect and this inhibition is partially mediated by cholinergic mechanism.