Lazarev Mark, Lamb Janette, Barmada M Michael, Dai Feng, Anderson Michelle A, Max Mitchell B, Whitcomb David C
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Mol Pain. 2008 Nov 17;4:58. doi: 10.1186/1744-8069-4-58.
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).
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.
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.
疼痛常常是慢性胰腺炎的主要临床特征,但不同个体间疼痛的频率和严重程度差异很大。我们推测基因多态性导致了临床疼痛模式的差异。由于据报道鸟苷三磷酸环化水解酶(GCH1)基因的遗传变异可使一些患者免受疼痛困扰,我们在北美胰腺炎研究2(NAPS2)中,对特征明确的慢性胰腺炎(CP)或复发性急性胰腺炎(RAP)患者,研究了“疼痛保护性单倍型”的作用。
NAPS2研究中的受试者被要求将其疼痛程度分为反映不同疼痛频率和严重程度水平的5类中的一类。对所有受试者进行rs8007267和rs3783641基因分型,以确定GCH1疼痛保护性单倍型的频率。在白种人受试者中,对照组(n = 236)、CP患者(n = 265)、RAP患者(N = 131)或按疼痛类别分类的CP患者中,疼痛保护性GCH1单倍型的频率与之前报道的一般白种人群中的单倍型频率相比无差异。
GCH1疼痛保护性单倍型对RAP或CP的疼痛模式或严重程度没有显著影响。这些结果对于帮助确定内脏痛的调节因子以及区分不同的疼痛机制具有重要意义。