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Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?

Lazarev M, Lamb J, Barmada MM, Dai F, Anderson MA, Max MB, Whitcomb DC - Mol Pain (2008)

Bottom Line: In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236), CP patients (n = 265), RAP patients (N = 131), or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population.The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP.These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. markglazarev@yahoo.com

ABSTRACT

Background: Pain is often a dominant clinical feature of chronic pancreatitis but the frequency and severity is highly variable between subjects. We hypothesized that genetic polymorphisms contribute to variations in clinical pain patterns. Since genetic variations in the GTP cyclohydrolase (GCH1) gene have been reported to protect some patients from pain, we investigated the effect of the "pain protective haplotype" in well characterized patients with chronic pancreatitis (CP) or recurrent acute pancreatitis (RAP) from the North American Pancreatitis Study 2 (NAPS2).

Results: Subjects in the NAPS2 study were asked to rank their pain in one of 5 categories reflecting different levels of pain frequency and severity. All subjects were genotyped at rs8007267 and rs3783641 to determine the frequency of the GCH1 pain-protective haplotype. In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236), CP patients (n = 265), RAP patients (N = 131), or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population.

Conclusion: The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP. These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.

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Related in: MedlinePlus

Pain-protective haplotype frequency in CP by pain type. The frequency of the "pain protective haplotype" as percentage of total counts in the CP group subdivided by the subject's response to the pain question. * P = 0.02 comparing group D compared to controls. This was in the opposite direction that was hypothesized, and the value became non-significant after Bonferroni corrected for multiple testing. No other significant differences were detected. "Pain protective haplotype" counts: A = 13, B = 8, C = 32, D = 40, E = 5, Controls = 67.
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Figure 3: Pain-protective haplotype frequency in CP by pain type. The frequency of the "pain protective haplotype" as percentage of total counts in the CP group subdivided by the subject's response to the pain question. * P = 0.02 comparing group D compared to controls. This was in the opposite direction that was hypothesized, and the value became non-significant after Bonferroni corrected for multiple testing. No other significant differences were detected. "Pain protective haplotype" counts: A = 13, B = 8, C = 32, D = 40, E = 5, Controls = 67.

Mentions: The demographic results for the subjects are presented in Table 2. Using fastPHASE, the common haplotype (GA), the uncommon haplotype (AT – also known as the "pain-protective haplotype"), and other less common haplotypes were determined. Fisher's exact test for the GA and AT haplotypes in RAP and CP versus controls was performed and the p-values recorded. Table 3 shows the haplotype frequencies for all patients, CP patients, RAP patients, healthy controls, as well as the corresponding p-value. Table 4 shows a subdivision of all patients, CP patients, and RAP patients into different pain groups. The only significant finding is the CP patients with group D pain pattern, who were more likely to possess the uncommon AT haplotype in comparison to controls p = 0.02 (OR = 1.69; CI 1.06–2.68)) which became non-significant after Bonferroni corrected for multiple testing. Allelic frequencies of the AT haplotype are graphically displayed for all groups (Figure 1), among different pain groups (Figure 2), and for chronic pancreatitis patients (Figure 3).


Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?

Lazarev M, Lamb J, Barmada MM, Dai F, Anderson MA, Max MB, Whitcomb DC - Mol Pain (2008)

Pain-protective haplotype frequency in CP by pain type. The frequency of the "pain protective haplotype" as percentage of total counts in the CP group subdivided by the subject's response to the pain question. * P = 0.02 comparing group D compared to controls. This was in the opposite direction that was hypothesized, and the value became non-significant after Bonferroni corrected for multiple testing. No other significant differences were detected. "Pain protective haplotype" counts: A = 13, B = 8, C = 32, D = 40, E = 5, Controls = 67.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2626574&req=5

Figure 3: Pain-protective haplotype frequency in CP by pain type. The frequency of the "pain protective haplotype" as percentage of total counts in the CP group subdivided by the subject's response to the pain question. * P = 0.02 comparing group D compared to controls. This was in the opposite direction that was hypothesized, and the value became non-significant after Bonferroni corrected for multiple testing. No other significant differences were detected. "Pain protective haplotype" counts: A = 13, B = 8, C = 32, D = 40, E = 5, Controls = 67.
Mentions: The demographic results for the subjects are presented in Table 2. Using fastPHASE, the common haplotype (GA), the uncommon haplotype (AT – also known as the "pain-protective haplotype"), and other less common haplotypes were determined. Fisher's exact test for the GA and AT haplotypes in RAP and CP versus controls was performed and the p-values recorded. Table 3 shows the haplotype frequencies for all patients, CP patients, RAP patients, healthy controls, as well as the corresponding p-value. Table 4 shows a subdivision of all patients, CP patients, and RAP patients into different pain groups. The only significant finding is the CP patients with group D pain pattern, who were more likely to possess the uncommon AT haplotype in comparison to controls p = 0.02 (OR = 1.69; CI 1.06–2.68)) which became non-significant after Bonferroni corrected for multiple testing. Allelic frequencies of the AT haplotype are graphically displayed for all groups (Figure 1), among different pain groups (Figure 2), and for chronic pancreatitis patients (Figure 3).

Bottom Line: In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236), CP patients (n = 265), RAP patients (N = 131), or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population.The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP.These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. markglazarev@yahoo.com

ABSTRACT

Background: Pain is often a dominant clinical feature of chronic pancreatitis but the frequency and severity is highly variable between subjects. We hypothesized that genetic polymorphisms contribute to variations in clinical pain patterns. Since genetic variations in the GTP cyclohydrolase (GCH1) gene have been reported to protect some patients from pain, we investigated the effect of the "pain protective haplotype" in well characterized patients with chronic pancreatitis (CP) or recurrent acute pancreatitis (RAP) from the North American Pancreatitis Study 2 (NAPS2).

Results: Subjects in the NAPS2 study were asked to rank their pain in one of 5 categories reflecting different levels of pain frequency and severity. All subjects were genotyped at rs8007267 and rs3783641 to determine the frequency of the GCH1 pain-protective haplotype. In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236), CP patients (n = 265), RAP patients (N = 131), or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population.

Conclusion: The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP. These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.

Show MeSH
Related in: MedlinePlus