Pi Polymorphism Research Articles

Glutathione S-transferase pi polymorphism contributes to the treatment outcomes of advanced non-small cell lung cancer patients in a Chinese population.

We analyzed the association between polymorphisms in three glutathione S-transferase genes (GSTP1, GSTM1, and GSTT1) and the treatment outcome for advanced non-small cell lung cancer (NSCLC). We recruited 284 NSCLC patients at advanced stage from Department of Radiotherapy in Peace Hospital Attached to Changzhi Medical College between May 2009 and May 2011, who had received cisplatin-based chemotherapy. The GSTP1, GSTM1, and GSTT1 genotyping for was determined using DNA pyrosequencing on an ABI Prism 3100 DNA analyzer. In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes of GSTP1 were associated with lower risk of disease progression compared with the IIe/IIe genotype, and the HRs (95%CIs) were 0.37 (0.18-0.74) and 0.15 (0.06-0.35), respectively. The IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with NSCLC, and the HRs (95%CIs) were 0.52 (0.29-0.92) and 0.37 (0.17- 0.79), respectively No significant association was observed between GSTM1 and GSTT1 polymorphisms and progression-free survival and overall survival in the NSCLC patients. In summary, we suggest that GSTP1 polymorphisms might influence the treatment outcome of advanced NSCLC patients, and our results could help improve individualized therapy.

The relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 and glutathione S transferase Pi polymorphisms

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients’ cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

Studies on the Polymorphism of Thiaminase I in Seawater Fish

Thiaminase I from the seawater fish Fisturalia petimba was characterized, and pI polymorphism of the enzyme was first described, together with the active subfragment of thiaminase I. The liver of F. petimba contained thiaminase I of at least three different pIs and the major fraction exhibited pI 5.7. The most evident difference among pI isozymes was the size of the active subfragments into which they were dissociated. pI 5.7 enzyme dissociated into subfragments of 25 kDa, while pI 7-9 enzymes dissociated into approx. 22 kDa. The reaction rate measured by pyridine as the second substrate was three times higher in pI 7-9 enzymes compared with pI 5.7 enzyme. The degree of cadmium inhibition, when aniline was the co-substrate, also showed obvious differences between pI isozymes. When the major pI fraction was further purified by the difference in hydrophobicity, a smaller active fragment of approx. 22 kDa appeared, indicating the possibility that the difference in the size of active subfragment between isozymes is a result of partial fragmentation. The pI 5.7 enzyme was purified 250 times and the size of the most purified preparation was found to be 106 kDa by gel filtration analysis. The purified preparation gave an active 25 kDa subfragment by SDS-PAGE, together with a 15 kDa non-active subfragment. The enzyme was, thus, inferred to contain active subfragments together with the 15 kDa non-active fragments. Amino acid sequencing of the 25 kDa active subfragment revealed, together with the fully processed N-terminal sequence, two N-terminal peptides with extra Pro-Ser and Gly-Pro-Ser attached to it, and the NCBI non-redundant database did not show significant similarity to other known proteins. On the other hand, the molecular mass of the holoenzyme from the viscera of the seawater fish Engraulis japonica was estimated to be approx. 100 kDa by gel filtration chromatography. An SDS-PAGE analysis revealed that it contained an active subfragment of 22 kDa.

Alpha 1 antitrypsin polymorphism in the tunisian population with special reference to pulmonary disease

The study investigated alpha 1 antitrypsin (AAT) gene polymorphism in the Tunisian population. We aimed to analyze the correlation between Pi polymorphism and the risk of developing chronic obstructive pulmonary disease (COPD). We focused our study on two samples originating from the Tunisian centre: 318 healthy controls and 90 patients suffering from COPD. Data analysis was investigated by AAT level quantification, serum isoelectric focusing (IEF) and RFLP-PCR performed with PiS and PiZ allele specific primers. We calculated PiM1, PiM2, PiM3, PiS and PiZ allele frequencies in patients and controls. The difference in allele frequencies is significant only for the PiM2 allele (P=0.00378). In COPD patients, we note the presence of PiZ allele. This allele mainly observed in European populations, is rare in sub-Saharian populations and not described in North Africa. PiZ allele is found in COPD sample and never in Tunisian controls. However, no significant difference in PiZ allele frequency between patients and controls can be concluded. PiM2 allele, which is considered as "normal" variant can be associated with COPD risk.

PI polymorphism in Israel: Report on six Jewish population groups

A total of 1148 Israeli Jews was typed for PI and divided by areas of origin into six groups: Eastern Europe (n = 236), Central Europe (n = 156), Rumania (n = 158), Bulgaria (n = 215), North Africa (n = 229), and Middle East (n = 154). Frequencies of PI*M1 (0.74-0.77) in Jews of European countries were higher than 0.68 in Jews of N. Africa and 0.62 in Jews of the Middle East. PI*M2 frequencies were correspondingly lower in European Jews: 0.11-0.14 vs 0.19 and 0.20 in non-European Jews. PI*M3 frequency range was 0.07-0.11 in European Jews and was highest in Middle Eastern Jews (0.17). PI*Z was found in one MZ individual. PI*S was low (less than 0.01) except in Sephardi Jews of Bulgaria and N. Africa (0.016 and 0.015). A rare variant, PI*Elemberg, was observed in five individuals from different countries of origin. The present results are in accord with those of a previous study on some Israeli Jewish groups and on some other Middle Eastern groups.

Distribution of Hp, Tf, Gc and Pi Polymorphisms in a Japanese Population Sample from San-in District

Distribution of Hp, Tf, Gc and Pi systems was studied in 225 serum samples from a Japanese population in the central region of San-in District of Japan. The frequencies of Hp1, TfC1 and PiM1 alleles were found to be somewhat but not significantly low as compared with other Japanese populations. A new variant type of Gc was observed to be located between the Gc 1S and 1C2 bands. The obtained gene frequencies are as follows: Hp1=0.2183, Hp2=0.7817; TfC1=0.7448, TfC2=0.2456, TfVar=0.0096; Gc1F=0.4411. Gc1S=0.2823, Gc2=0.2645, Gc1A2=0.0121; PiM1=0.6742, PiM2=0.2793, PiM3=0.0465.

Distribution of Hp, Tf Gc and Pi Polymorphisms in a Nepalese Population

Hp typing and Tf, Gc and Pi subtypings were performed on 144 serum samples from a Nepalese population in the Katmandu Valley, Nepal. The obtained allele frequencies are as follows: Hp1 = 0.1771, Hp2 = 0.8229; TfC1 = 0.7222, TfC2 = 0.2500, TfC3 = 0.0174, TfCnepal (TfC9) = 0.0104; Gc1F = 0.2448, Gc1S = 0.4825, Gc2 = 0.2727; PiM1 = 0.6076, PiM2 = 0.2118, PiM3 = 0.1806. The relationship between this sample population and the Indian population is discussed.

Pi M4: an additional Pi M subtype.

The authors studied Pi polymorphism using the Separator isofocusing method with slight modification. A new Pi allele was observed. Family pedigrees confirmed co-dominant inheritance with other Pi alleles. According to the electrophoretic mobility of its isoprotein bands, and to its frequency (0.04) this new allele is considered as a fourth Pi M subtype: Pi M4.

7.5. Investigations on the Pi polymorphism in a German population — Evidence for two new rare alleles, Pi T and Pi

7.5. Investigations on the Pi polymorphism in a German population — Evidence for two new rare alleles, Pi T and Pi <L

Reliable Classification of Six Pi M Subtypes by Separator Isoelectric Focusing

For the first time, segregation of three common PiM alleles in family material is verified by application of separator isoelectric focusing. A new nomenclature system for the Pi M subtypes is used, whereby the common subtypes are designated according to their physicochemical properties; the most anodal type is called Pi M1, the intermediary one Pi M2, and the most cathodal variant Pi M3 (previously called Pi M2). Pi gene frequencies from Finnish, Dutch and Black populations are presented. The PiM2 allele was rather high in Finns (0.12) but low (0.04) in the West African Bozo. The PiM3 was found with a frequency of 0.13 in Dutch, 0.08 in Finns and 0.02 in Bozo. A previous Finnish sample was retested with the new subtyping method and the six-subtype distribution was found to be in good Hardy-Weinberg equilibrium. The validity of the Pi polymorphism for population genetics, linkage analysis and parentage testing is discussed.