Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations.

BACKGROUND & AIMS: Nonalcoholic chronic pancreatitis is usually idiopathic and often associated with cystic fibrosis gene (CFTR) mutations. It is unknown whether pancreatitis risk correlates with having 1 or 2 CFTR mutations, abnormal epithelial ion transport, or mutations of other genes. METHODS: We tested 39 patients with idiopathic chronic pancreatitis (mean age at diagnosis, 33 years) for common mutations of CFTR and of genes encoding a trypsin inhibitor (PSTI) and trypsinogen (PRSS1). To exclude hereditary pancreatitis, we initially relied on family history and subsequently tested for PRSS1 mutations. Twenty subjects were tested for rare CFTR mutations (DNA sequencing) and 11 were tested for extrapancreatic CFTR function (clinical and physiologic evaluation). RESULTS: Mutations were identified in 24 of 39 subjects. Nine patients had cystic fibrosis-causing mutations, 8 of whom also had mild-variable mutations. Eight others had only mild-variable mutations. Nine subjects had the N34S PSTI mutation and 1 had hereditary pancreatitis (R122H, PRSS1). Pancreatitis risk was increased approximately 40-fold by having 2 CFTR mutations (P < 0.0001), 20-fold by having N34S (P < 0.0001), and 900-fold by having both (P < 0.0001). Subjects with 2 CFTR mutations had abnormal nasal epithelial ion transport and clinical findings suggesting residual CFTR function between that in cystic fibrosis and in carriers. By contrast, subjects with only PSTI mutations had normal CFTR function. CONCLUSIONS: CFTR-related pancreatitis risk correlates with having 2 CFTR mutations and reduced extrapancreatic CFTR function. The N34S PSTI mutation increased risk separately. Testing for pancreatitis-associated CFTR and PSTI genotypes may be useful in nonalcoholic pancreatitis.     

Genetic analysis of the glutathione s-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis

Background Specific mutations in the cationic trypsinogen gene (PRSS1) are disease-causing in patients with hereditary pancreatitis, but the genetic background still remains mysterious in about 40% of patients with the disease. It has been suggested that oxidative stress contributes to pancreatic damage. The glutathione s-transferases (GSTs) represent major detoxification enzymes that protect cells from oxidative stress.Methods In the present study we tested whether mutations in the MGST1 and GSTM3 genes or common deletions in the GSTT1 and GSTM1 genes are associated with hereditary pancreatitis. We analyzed the entire coding region of MGST1 and GSTM3 in 30 patients that were tested negative for PRSS1 mutations, and we studied 55 controls. For GSTT1 and GSTM1, we investigated 75 hereditary pancreatitis patients who had been tested negative for PRSS1 mutations, 135 hereditary pancreatitis patients with a PRSS1 mutation, and 183 controls. Patients were further subclassified with regard to age of onset of disease as a marker of severity.Results No mutation was found in the MGST1 gene. In the GSTM3 gene, we detected a homozygous 670G > A polymorphism (V224I) with similar frequencies in patients and controls. We found no difference in the frequencies of the GSTT1 and GSTM1 null genotypes between patients and controls, and we detected no differences in age of onset in patients with or without GSTT1 and GSTM1 deletions.Conclusions We conclude that genetic alterations in the MGST1, GSTM3, GSTT1, and GSTM1 genes do not play a dominant role in hereditary pancreatitis.     

Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments for the motion.

Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the pancreatic secretory trypsin inhibitor (PSTI) or serine protease inhibitor, Kazal type 1 (SPINK1) gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of the PRSS1 gene, which can be readily identified by genetic testing. Mutations of the CFTR gene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of the SPINK1 (or PSTI) gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of the PRSS1 and SPINK1 genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests that SPINK1 is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.     

Motion--genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: arguments against the motion.

Mutations of two genes, the cystic fibrosis transmembrane conductance regulator gene (CFTR) and the pancreatic secretory trypsin inhibitor gene (PSTI), are associated with an increase in the risk of idiopathic chronic pancreatitis. Persons who have mutations of both CFTR alleles (one severely and one mildly affected) are especially susceptible to this disease. Because these compound heterozygotes have sufficient residual CFTR function, they do not develop cystic fibrosis lung disease. One PSTI mutation, N34S, independently increases the risk of pancreatitis. Thus, the risk of pancreatitis is greatest among individuals who are CFTR compound heterozygotes and who also have the PSTI mutation. Nonetheless, most people with CFTR and PSTI mutations do not develop pancreatitis. This fact indicates that environmental influences and gene-gene interactions also affect pancreatitis risk. Although CFTR and PSTI genetic testing can identify persons at an increased risk of pancreatitis, there are several reasons why the routine screening of individuals with nonhereditary pancreatitis is not recommended at this time: most disease-associated mutations are not detected by readily available techniques, genetic counselling guidelines do not exist, most patients with mutations do not develop pancreatitis and the results of testing do not affect the clinical management of pancreatitis.     

Recurrent acute and chronic pancreatitis in two brothers with familial chylomicronemia syndrome

The chylomicronemia syndrome is well recognized as a rare etiologic factor of acute pancreatitis; however, whether hypertriglyceridemia can cause chronic pancreatitis (CP) remains unclear. We describe the long-time course of 2 brothers with the familial chylomicronemia syndrome caused by identical compound heterozygous mutations in the lipoprotein lipase (LPL) gene with markedly reduced LPL activity. Other etiologic factors were excluded, including mutations in the PRSS1, SPINK1, and CFTR gene. Although both brothers had recurrent acute pancreatitis and the same LPL genotype, CP became evident in only one patient. Progression to CP was associated with a more severe disease course. Thus, the chylomicronemia syndrome may cause CP in the absence of other known causative factors, and similar to alcoholic and hereditary CP, a more severe disease course is associated with disease progression.     

Hereditary chronic pancreatitis

Hereditary chronic pancreatitis (HCP) is a very rare form of early-onset chronic pancreatitis. Apart from young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. Diagnostic criteria and treatment of HCP also resemble those of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile-duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, the disease is mild in most patients. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation, disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes--such as the anionic trypsinogen (PRSS2), the serine protease inhibitor Kazal type 1 (SPINK1), and the cystic fibrosis transmembrane conductance regulator (CFTR)--have also been found to be associated with chronic pancreatitis (idiopathic and hereditary). Genetic testing should only be performed in carefully selected patients by direct DNA sequencing, and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications such as pseudocysts and bile-duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. The risk of pancreatic cancer is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.     

Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase M1 'null' mutation

BACKGROUND: Pathogenesis and genetic factors influencing predisposition to antituberculosis drug (ATD)-induced hepatotoxicity are not clear. Polymorphism at the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N-acetyltransferase type 2 (NAT2), is reported to be associated with the excess generation of toxic reactive metabolites. Polymorphisms at the glutathione S-transferase (GST) loci (GSTM1 and GSTT1) are involved in the detoxification of these toxic metabolites in the human body to a lesser extent. We have examined whether polymorphisms at these loci are associated with the risk of ATD-induced hepatotoxicity. METHODS: In this case-control study, 33 pulmonary tuberculosis patients with ATD-induced hepatotoxicity and 33 pulmonary tuberculosis patients receiving ATD drugs without any evidence of hepatotoxicity were considered as cases and controls, respectively. Point mutations at NAT2 and homozygous 'null' mutations at GSTM1 and GSTT1 genes were looked into genomic DNA, isolated from peripheral blood mononuclear cells by using polymerase chain reaction (PCR). RESULTS: The frequency of homozygous 'null' mutation at the GSTM1 gene was significantly higher among cases (n = 17, 52%) than controls (n = 8, 24%) (P < 0.05, relative risk 2.13, 95% CI: 1.25-3.10). Frequencies of mutations at GSTT1 and NAT2 genes did not differ significantly between cases and controls. CONCLUSION: Homozygous 'null' mutation at the GSTM1 gene might predispose an individual to ATD-induced hepatotoxicity.     

Association of NAT and GST polymorphisms with non-Hodgkin's lymphoma: a population-based case-control study

Several chemicals have been associated with risk of non-Hodgkin's lymphoma (NHL), many of which are substrates for N-acetyltransferase (NAT) and glutathione S-transferase (GST) enzymes. We investigated the association between polymorphisms in genes coding for these enzymes and NHL risk in a population-based study (389 cases and 535 controls). NAT1 slow genotype was associated with a slightly increased risk in women [odds ratios (OR) = 1.4; 95% confidence interval (CI) = 0.9-2.3], but not in men. NAT2 slow genotype was not associated with risk in either sex. The two slow genotypes of NAT1 and NAT2 combined were associated with a minor increase of risk in women (OR = 1.4; 0.8-2.4). There was no association with the GSTM1 or GSTT1 null genotype in either sex, irrespective of histological subtypes. Individuals with GSTP1 Val homozygotes had non-significant excessive risk of marginal zone lymphoma (OR = 1.8; 0.6-5.1) and 'other' B-cell NHLs (OR = 1.6; 0.7-3.6), but lower risk of diffuse large B-cell lymphoma (OR = 0.2; 0.1-0.96). Risk did not elevate with an increasing number of high-risk GST alleles in either sex. In summary, although NAT1, NAT2, GSTM1, GSTT1, or GSTP1 polymorphisms do not appear to be associated with NHL risk overall, there might be gender-specific and subtype-specific associations that require confirmation.     

慢性胰腺炎候选易感基因的研究进展

已发现阳离子胰蛋白酶原（PRSS1）基因、囊性纤维化跨膜传导调节因子（CFTR）基因和胰分泌性胰蛋白酶抑制剂Kaza11型（SPINK1）基因突变可显著提高个体对慢性胰腺炎（CP）的易感性。大量研究结果显示CTRC基因很可能为CP易感基因研究的新热点;TNF-238A基因、UGT1A7基因、CASR基因或乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）2及羧基酯脂肪酶（CEL）等与酒精代谢有关的基因等亦被认为有较好研究前景;GSTT-1＊A和角蛋白8的作用尚难界定;而血色素沉着症基因（HFE）、二氧化锰超氧化剂物歧化酶（MnSOD）和谷胱甘肽转移酶同工酶（GSTP1）基因很可能与CP无关。但这仅仅是研究的开始,为彻底阐明CP易感基因之谜尚需付出巨大努力。     

Polymorphism in alcohol-metabolizing enzymes, glutathione S-transferases and apolipoprotein E and susceptibility to alcohol-induced cirrhosis and chronic pancreatitis

BACKGROUND AND AIM: Susceptibility to organ damage induced by alcohol may be due to inherited variation (polymorphism) in ethanol-metabolizing enzymes, or to polymorphisms affecting free radical or lipid metabolism mediated by enzymes such as glutathione S-transferases and apolipoprotein E. The aim was to compare the genotype frequencies of alcohol dehydrogenase-2 (ADH2), ADH3, aldehyde dehydrogenase-2 (ALDH2), cytochrome P450-2E1 (CYP2E1), glutathione S-transferase-M1 (GSTM1), GSTT1, and apolipoprotein E in patients with alcoholic cirrhosis and alcoholic chronic pancreatitis to those in control groups. PATIENTS AND METHODS: The case-control study was restricted to Caucasian adults: 57 with alcoholic cirrhosis, 71 with alcoholic chronic pancreatitis, 57 alcoholics without apparent organ damage and 200 healthy blood donors. Genotypes were determined by restriction fragment length polymorphism after amplification of genomic DNA by polymerase chain reaction. RESULTS: The genotype ADH3*2/*2 was more frequent in patients with cirrhosis (40%) than blood donors (12%; OR 4.92, 95% CI 2.36-10.31) and patients with chronic pancreatitis (8%; OR 7.33, 95% CI 2.54-23.78) but was not significantly different from alcoholic controls (23%; OR 2.27, 95% CI 0.95-5.66). Patients with cirrhosis also had a higher frequency (P < 0.05) of ADH2*1/*1 (100%) than blood donors (92%) and those with chronic pancreatitis (93%). The frequencies of genotypes of ALDH2, CYP2E1, GSTM1, GSTT1 and apolipoprotein E were similar in all groups. CONCLUSION: Alcoholic cirrhosis but not alcoholic chronic pancreatitis is associated with ADH3*2/*2 and perhaps with ADH2*1/*1. Both genes encode less active alcohol-metabolizing enzymes that may be associated with cirrhosis because of delayed formation of acetaldehyde (with higher intakes of alcohol), or diversion of alcohol metabolism through pathways other than ADH.     

Genetic counseling for hereditary pancreatitis--the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1

The importance of pretest information, using an accredited DNA laboratory and interpreting the genotype on behalf of the patient and their physicians is emphasized. Care with predictive testing and the strong encouragement to involve a specialist genetic counseling service is made. A similar approach to genetic testing should be used when children are involved. Because of the incomplete pickup of PRSS1 mutations, particularly of a limited mutation panel of R122H and N291 (perhaps with A16V), a diagnosis of HP cannot be ruled out by molecular genetic testing alone. The A16V mutation has a reduced penetrance, and its contribution to pancreatitis remains unclear. The advice to patients with genetic forms of pancreatitis is a strong encouragement to avoid smoking, to avoid alcohol, and to remain in contact with clinical and research groups for their follow-up and screening trials for early pancreatic cancer. The remaining issues are of how wide to cast the net of investigation in patients with unexplained pancreatitis, particularly looking for mutations in the CFTR and lower penetrance genes such as PSTI/SPINK1.     

Mutations of SPINK1 and PRSS1 gene in Korean patients with chronic pancreatitis]

BACKGROUND/AIMS: It has been found that mutations of cationic trypsinogen gene (PRSS1) and serine protease inhibitor, Kazal type 1 gene (SPINK1) increase the susceptibility of chronic pancreatitis (CP). Specifically, mutations in the PRSS1 gene are related to the occurrences of hereditary and idiopathic pancreatitis while SPINK1 mutations are known to act as a disease modifier and are associated with idiopathic CP. However, the association of SPINK1 mutations with alcoholic CP is still controversial. We investigated the prevalence of PRSS1 and SPINK1 mutations in idiopathic and alcoholic CP in Korea. METHODS: Seventy-one Korean patients with CP (alcoholic: 47, idiopathic: 22 and familial: 2) and 19 controls were included in this studies. Genomic DNA was extracted from peripheral blood of the patients. Mutations of SPINK1 (exon 3: N34S) and PRSS1 (exon 2: N29I, exon 3: R122H) genes were detected by PCR-RFLP methods. For the detection of SPINK1 mutation, restriction endonuclease PstI and BsrDI were used, while Sau3A and AflIII were used for the defection of PRSS1 mutation. RESUTLS: Only one patient (2.1%) with alcoholic CP was a heterozygote for SPINK1 (N34S) mutation. Mutation in the PRSS1 (N29I, R122H) gene was not found in any group of CP patients. Additionally, we could not find any mutations of SPINK1 or PRSS1 in the control group. CONCLUSIONS: SPINK1 and PRSS1 mutations are not related to the development of CP in Korea.     

Association of Genetic Polymorphism of GSTT1, GSTM1 and GSTM3 in COPD Patients in a North Indian Population

Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). Cigarette smoking is the main etiological factor for decline in lung function in COPD. However, only 10–20% chronic smokers develop symptomatic COPD. Genetic susceptibility to COPD might depend upon the variation of enzyme activities that detoxify cigarette smoke components. We performed a case control study to assess the association of Glutathione- S-transferase T1(GSTT1),Glutathione- S-transferase M1 (GSTM1), and Glutathione-S-transferase M3(GSTM3) common polymorphisms with the susceptibility to COPD patient in a north India population. In the present study, the genotypes of 412 subjects, (204 COPD patients and 208 healthy controls) were analyzed. Statistical analysis revealed that the frequency of homozygous GSTM1 null genotype was found to be significant higher in COPD patients as compared with healthy controls (OR, 2.58; 95% CI, 1.73–3.84; P = 0.001), but there were no significant differences in the distribution of homozygous null GSTT1 and 3-bp deletion polymorphism (rs1799735) in intron 6 variant allele in GSTM3 between COPD patients and healthy controls. Our study results suggest that GSTM1 null polymorphism is associated with genetic susceptibility to COPD. Moreover, we also found association between this polymorphism with pulmonary function test in smokers as well as nonsmokers.     

Genetic predisposition to alcoholic chronic pancreatitis

The mechanisms leading to alcoholic chronic pancreatitis in humans have remained elusive. Numerous questions surround the apparent random nature of the disease in which 1 person is hit with alcoholic chronic pancreatitis while the next is spared. Why do fewer than 10% of chronic, heavy alcohol users ever develop pancreatitis, while others develop alcoholic liver disease, neuropathy, or other alcohol-associated problems? Why do laboratory animals, fed large amounts of alcohol for prolonged periods of time, fail to develop typical chronic pancreatitis? Why are heavy alcohol users from a black African background more likely to develop pancreatic diseases than Caucasians, whereas the opposite is true for the development of liver disease? The answers underlying these questions appear to reflect the differences in underlying genetic susceptibility, environmental exposure, and the interaction between these factors. Thus, even cases of "typical" alcoholic chronic pancreatitis or other forms of pancreatitis appear to be complex diseases. Recently, several genetic mutations have been identified that increase the susceptibility to pancreatitis. However, the major common gene mutations in CFTR, PRSS1, and SPINK1 only slightly increase the risk of alcoholic chronic pancreatitis. New genetic, environmental, and triggering factors must be considered to gain further insight into the mechanisms leading to alcoholic chronic pancreatitis so that strategies for treatment and prevention can be developed.     

谷胱甘肽S-转移酶M1、T1基因多态与散发性大肠腺癌遗传易感性

目的　探讨谷胱甘肽S 转移酶 (GST)M1、T1基因多态与散发性大肠腺癌 (SCRAC)遗传易感性的关联。方法　应用多重聚合酶链反应 (PCR)技术 ,对经病理组织学确诊的 10 4例SCRAC患者及同期在本院体检的无血缘关系的 10 1例健康人 ,检测其GSTM1和GSTT1基因多态性。结果　 (1)在健康人和SCRAC患者 ,GSTM1、GSTT1空白基因型的频率差异均无显著性 (前者 4 6 5 % :5 6 7% ,χ2 =2 13,P >0 0 5 ;后者 4 7 5 % :6 0 6 % ,χ2 =3 5 2 ,P >0 0 5 )。 (2 )GSTM1空白基因型频率在近端与远端SCRAC患者间、在老年与非老年SCRAC间的频率差异均无显著性 ;而GSTT1空白基因型的频率差异有显著性 (前者 4 4 4 % :6 6 2 % ,χ2 =3 97,P <0 0 5 ;后者 70 9% :4 9 0 % ,χ2 =5 2 1,P <0 0 5 )。 (3)GSTM1、GSTT1均为空白基因联合型的个体患SCRAC的危险性升高 4 33倍 (9 6 % :2 6 9% ,χ2 =7 89,ν =3,P <0 0 5 )。结论　单独的GSTM1或GSTT1空白基因型与SCRAC遗传易感性无关 ,但GSTT1空白基因型与远端SCRAC遗传易感性有关 ,且多见于老年患者。GSTM1、GSTT1均为空白基因的联合基因型是SCRAC的易感基因型。     

Glutathione-S-transferase （GSTM1, GSTrl） and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, large-scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using real-time PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Concomitant autoimmune and genetic pancreatitis leads to severe inflammatory conditions

Chronic pancreatitis characterized by an early onset should be extensively investigated including the search for a mutation of the PRSS1, SPINK-1 or CFTR genes and potential features of autoimmune pancreatitis. We here describe a case of chronic pancreatitis with an onset at a very young age in which a mutation of the PRSS1 and several features of autoimmune pancreatitis were identified.     

Serine protease inhibitor Kazal type 1 mutations and pancreatitis

In summary, SPINK1 is thought to play an important role in protecting the pancreas against excessive trypsinogen activation. SPINK1 mutations are associated with the development of acute and chronic pancreatitis and have been detected in all forms of chronic pancreatitis. The strong association of mutations in the PRSS1 gene and in the SPINK1 gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis. The N34S mutation represents the most frequently observed pancreatitis-associated SPINK1 variant. Because the SPINK1 N34S mutation is very common in the general population, it is unlikely that this mutation alone can initiate the development of chronic pancreatitis. Thus, it rather appears that in most patients with SPINK1-associated chronic pancreatitis, this genetic variant acts as disease modifier or within a polygenic model with other yet unidentified genes or environmental cofactors. The possible interaction of mutations in the SPINK1 gene with other pancreatitis-associated susceptibility genes has to be investigated in future research efforts. The most promising candidate gene for such an interaction is the CFTR gene, because genetic alterations within the CFTR gene are also common in the general population and already have been associated with chronic pancreatitis.     

新疆哈萨克族人群谷胱甘肽S转移酶M1、T1基因多态性

目的 探讨谷胱甘肽S转移酶M1、T1基因多态性在新疆哈萨克族人群中分布的特点.方法通过多重聚合酶链反应对新疆哈萨克族264例个体 GSTM1、GSTT1基因型进行检测.结果 GSTM1、GSTT1基因缺失型在新疆哈萨克族人群中频率分别为47%及36.4%,同时为GSTM1、GSTT1基因缺失型的频率为20.5%.结论 新疆哈萨克族人群GSTM1、GSTT1基因多态性与汉族及其他少数民族存在一定差异.     

Polymorphisms of glutathione S-transferase genes and functional activity in smokers with or without COPD.

OBJECTIVE: To determine the role of polymorphisms of genes regulating glutathione S-transferase (GST) and its plasma GST activity in the pathogenesis of chronic obstructive pulmonary disease (COPD). DESIGN: Case-control study. METHODS: One hundred and sixty-three patients with stable COPD from several community or regional hospitals were matched for age and pack-years smoked with the same number of health controls from the general population. Each participant underwent an interview-based respiratory and smoking questionnaire, lung function testing and gave a blood sample. Genotyping was carried out using a polymerase chain reaction-based method for polymorphisms of glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase P 1 (GSTP1) genes. Plasma GST activity was measured using the spectrofluorometric method. RESULTS: There were no significant differences in the distribution of various genotypes of polymorphisms of GSTT1, GSTM1 and GSTP1 between COPD patients and healthy controls. GST activity was significantly higher in patients compared with controls, irrespective of their different genotypes, and was not different between patients with different levels of airflow obstruction. CONCLUSION: Polymorphisms of GSTT1, GSTM1 and GSTP1 genes are unlikely to be involved in the pathogenesis of COPD in Chinese in Hong Kong and Southern China.