Genetic Polymorphisms In Patients Research Articles

Analysis of HSPA1B (+1267A>G) Genetic Polymorphism in Patients with Vibration Disease in Combination with Metabolic Syndrome.

In 167 men with vibration syndrome (VS), allele and genotype frequencies of HSPA1B (+1267A>G) genetic polymorphism (rs1061581) were studied depending on the type of vibration exposure and on the presence or absence of metabolic syndrome (MetS). The examined subjects were divided into two groups: VS patients (n=80) and VS+MetS patients (n=87). The differences in the lipid profiles between groups were revealed against the background of the lack of distinctions in the age of patients for A/G and G/G genotypes carriers. An increase in A/A (p=0.03) and a decrease in A/G (p=0.04) genotype frequencies in VS patients caused by hand-transmitted vibration in comparison with those in whom the disease was caused by a combination of hand-transmitted and whole-body vibration were found. The shifts in the frequencies of the above genotypes (p=0.01) were similar in patients with both types of vibration exposure in the VS+MetS group in comparison with VS group; the carriage of genotypes with the G allele in VS group exceeded that in VS+MetS group (p=0.01).

Associations among plasma concentrations of regorafenib and its metabolites, adverse events, and ABCG2 polymorphisms in patients with metastatic colorectal cancers.

The association between the pharmacokinetics and pharmacodynamics of regorafenib, a multiple tyrosine kinase inhibitor, remains unclear. This study assessed the trough plasma concentrations (Ctrough) of regorafenib and its N-oxide (M2) and N-oxide/desmethyl (M5)metabolites, and evaluated the associations among these levels, adverse events, and pharmacokinetic-related genetic polymorphisms in patients with metastatic colorectal cancer. The Ctrough levels of regorafenib and its metabolites were assessed in a single-center, prospective, observational study, 7days after the initial treatment. The correlation between those values and adverse events was then examined. In addition, the genetic polymorphisms of ABCG2, SLCO1B1, and UGT1A9 were determined and evaluated for associations with the levels of regorafenib, M2, and M5. We analyzed 43 patients who received regorafenib 40-120mg/day; among them, 35 patients started at 120mg/day. With regard to bilirubin increase, the Ctrough values of regorafenib were significantly higher in the group with grade ≥ 2 than in groups with grades 0 and 1 (p = 0.010). The M5 Ctrough levels were significantly associated with the severity of hypertension or rash (p < 0.05). In a multivariate analysis, the M5 Ctrough values and age were significant predictors of severe rash. Lastly, significant differences were noted in the M5 concentration-to-dose ratio values between the patients with ABCG2 421A/A and ABCG2 421C/A or C/C polymorphisms (p = 0.035). This study showed that the Ctrough of regorafenib was associated with bilirubin increase, and also clarified for the first time that the Ctrough of M5 was significantly correlated with hypertension and severe rash.

Effectiveness of personalized selection of antihypertensive therapy based on genetic polymorphism

Abstract Recent data indicate that it is important to develop the problem of genetic polymorphism in patients with arterial hypertension (AH) for the long-term possibility of using it as a justification for choosing the optimal treatment strategy. Currently, despite the availability of effective antihypertensive agents, the percentage of patients who have reached the target blood pressure level remains still not enough. A rational basis for choosing a particular class of drugs and / or their combinations in a concrete patient with AH can be the detection of genetic markers that determine the degree of sensitivity to therapy, since the relationship of its effectiveness with the genetic features is not in doubt today. Material and methods The work is based on the results of a clinical, instrumental, laboratory and genetic examination of 41 patients with AH with insufficient effectiveness of previous antihypertensive therapy. The median age and duration of the disease were 54 (32; 70) years and 7 (1; 20) years, respectively. Taking into account the identified gene polymorphism, a fixed combination of an ACE inhibitor (perindopril 10 mg) and a thiazide-like diuretic (indapamide 2.5 mg) was assigned. The comparative dynamics of blood pressure daily monitoring, left ventricle echocardiographic parameters, as well as indicators of vascular wall stiffness were analyzed before therapy and 3 months later. Results The study established a relationship between the clinical and morpho-functional features of AH in the examined patients with polymorphism of the AGT, AGTR2, CYP11B2, GNB3, NOS3 genes:-786 of their heterozygotes and “mutant” homozygotes, of which 3 polymorphic genes (AGT, AGTR2, CYP11B2) encode the activity of ACE. The obtained results allowed to establish that positive dynamics of the studied indicators was revealed in all patients. Though patients, carriers of the mutant allele C of polymorphic marker T704C AGT gene, had statistically significant more expressed benefit changes in blood pressure daily profile, echocardiographic parameters (such as left ventricular mass index, indicators of left ventricular diastolic function) and all parameters of arterial wall stiffness compared with patients who do not carry the “mutant” allele. Conclusion Thus, the selected treatment regimen demonstrated maximum antihypertensive, cardio - and vasoprotective effectiveness in the group of AH patients with the presence of the allele 704C of the polymorphic marker T704C of the AGT gene, which indicates the perspectivity of using genetic approaches to develop personalized tactics of AH patients drug treatment. Funding Acknowledgement Type of funding source: None

Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review.

Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a frequent and severe adverse drug reaction. Idiosyncratic responses due to genetic susceptibility to non-variceal UGIB has been suggested. A systematic review was conducted to assess the association between genetic polymorphisms and non-variceal UGIB. Twenty-one publications and 7134 participants were included. Thirteen studies evaluated genetic polymorphism in patients exposed to non-steroidal anti-inflammatory drugs, low-dose aspirin, and warfarin. Eight studies present at least one methodological problem. Only six studies clearly defined that the outcome evaluated was non-variceal UGIB. Genetic polymorphisms involved in platelet activation and aggregation, angiogenesis, inflammatory process, and drug metabolism were associated with risk of non-variceal UGIB (NOS3,COX-1; COX-2; PLA2G7; GP1BA; GRS; IL1RN; F13A1; CDKN2B-AS1; DPP6; TBXA2R; TNF-alpha; VKORC1; CYP2C9; and AGT). Further well-designed studies are needed (e.g., clear restriction to non-variceal UGIB; proper selection of participants; and adjustment of confounding factors) to provide strong evidence for pharmacogenetic and personalized medicine.

Enzyme activity and genetic polymorphisms in patients with type II diabetes mellitus

Diabetes mellitus (DM) has become more and more common and has a high morbidity and mortality rate worldwide. It is a multifactorial chronic disease affected by both genetic and environmental factors. To evaluate the association between antioxidant enzyme activities and their genetic variations and the level of malondialdehyde (MDA) in type II diabetes patients living in the Adıyaman province in the southeast part of Turkey. One hundred patients diagnosed with type II DM (T2DM) and 100 healthy controls were included in the study. Malondialdehyde levels and antioxidant enzyme activities were measured spectrophometrically. DNA isolation was performed and genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results revealed no significant differences in genotype distributions and allele frequencies of all polymorphisms between groups (p > 0.05). Significantly elevated MDA levels and a significant reduction in catalase (CAT) and paraoxonase (PON) enzyme activities were observed in patients compared to the control group in terms of study groups and genetic variations (p < 0.05). Moreover, CAT activity was reduced in TT genotype in terms of CAT -262 C/T polymorphism in patients (p < 0.05). Paraoxonase activity was observed to be lower in MM genotype in both groups (p < 0.05). CAT -262 C/T polymorphism may be one of the factors that lead to severe clinical situation in DM. Our results suggest that TT genotype may be more prone to lipid peroxidation.

ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy.

The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy. A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression. A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008-1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002-1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087-4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108-4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors. In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.

The impact of genetic polymorphisms on weight regain after successful weight loss.

Obesity is associated with an increased risk of various diseases and mortality. Although nearly 50 % of adults have been reported trying to lose weight, the prevalence of obesity has increased. One factor that hinders weight loss-induced decrease in obesity prevalence is weight regain. Although behavioural, psychological and physiological factors associated with weight regain have been reviewed, the information regarding the relationship between weight regain and genetics has not been previously summarised. In this paper, we comprehensively review the association between genetic polymorphisms and weight regain in adults and children with obesity after weight loss. Based on this information, identification of genetic polymorphism in patients who undergo weight loss intervention might be used to estimate their risks of weight regain. Additionally, the genetic-based risk estimation may be used as a guide for physicians and dietitians to provide each of their patients with the most appropriate strategies for weight loss and weight maintenance.

Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy.

Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients receiving current standard chemotherapy. The association between VIPN and genetic polymorphisms is largely unknown in adult lymphoma patients. To examine the possible relationship between known genetic polymorphisms in patients with pediatric acute lymphoblastic leukemia and incidence of VIPN in adult patients with B cell lymphoma, we examined CEP72 rs924607, ETAA1 rs17032980, MTNR1B rs12786200, CYP3A5 rs776746, rs7963521, and rs1045644 genetic polymorphisms in samples from 56 adult patients with B-cell lymphoma who received rituximab, cyclophosphamide, doxorubicin, VCR, and prednisone (R-CHOP) chemotherapy. Mutation analysis was performed by direct sequencing. The median age was 65years (range 30-79). The median cumulative dose of VCR was 12mg (range 2-16). VIPN was documented in 42 patients (75%), and 9 (16%) had grade 2-4 VIPN. Age, impaired glucose tolerance, number of cycles of R-CHOP, and VCR cumulative dose were not associated with incidence of VIPN. There was no association between the incidence of grade 2-4 or any grade VIPN and these six genetic polymorphisms. These results indicate that CEP72, MTNR1B, ETAA1, CYP3A5, rs7963521, and rs1045644 genetic polymorphisms are not associated with VIPN in patients with B-cell lymphoma who received R-CHOP.

Clinical Features of Visual Disturbances in Leiden Thrombophilia

The hereditary thrombophilias is a well-recognized important risk factor for a systemic and local thromboembolic events development. The case of Leiden thrombophilia family inheritance concomitant by the visual disturbances development are shown in this аrticle. Most commonly in hereditary thrombophilias, venous thrombembolias occur, arterial occlusions which have been reported in the recent literature only as individual clinical cases occur more rarely. In the European population hereditary thrombophilias are associated with a prothrombotic mutation in the coagulation factor V gene (Leiden factor) in a greater degree; herewith the risk of thrombotic complications is increasing significantly in homozygous polymorphism forms. Presence of combined mutations in several clotting factors also leads to risk of thrombembolias increase. Consequence of the Leiden mutation is a V activator resistance to the resolving action of the activated protein C which is a natural endogenous anticoagulant protein. Resistance development leads to a deceleration of V factor inactivation and to increasing of the thrombin amount. In the work presented here, development of the consistent bilateral occlusion of the central retinal artery (CRA) in a middle-aged patient with a heterozygous form of Leiden thrombophilia is the subject of interest. Along with the hereditary hemostatic system abnormality, the patient also had cardiovascular risk factors (hypertensive disease, atherosclerosis) which had a potentiating effect on the occlusion development. Taking into account the autosomal dominant nature of the Leiden mutation inheritance, the patient’s only daughter was examined; brief episodes of amaurosis fugax against the background of headaches similar to migraine were detected due to ophthalmological abnormalities. For verification of the Leiden thrombophilia diagnosis, both patients underwent molecular genetic diagnostics. Currently there are no large prospective studies showing the optimal and economically viable approach for identification of thrombophilia genetic polymorphisms in patients with retinal vascular occlusions in daily clinical experience. Possible additional risk factors for thrombembolias development, prevention services for manifest and recurrent vascular occlusions in patients with hereditary blood coagulation system abnormalities and their relatives are discussed in this article.

Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease

ObjectiveIn these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the IL1RN gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA....

EVALUATION OF INTERLEUKIN 6 POLYMORPHISMS AND ITS ASSOCIATION WITH RHEUMATOID ARTHRITIS IN BRAZILIAN WOMEN

Objective To verify the association between serum interleukin 6 (IL-6) levels and IL-6 genetic polymorphisms in patients with rheumatoid arthritis (RA), as well as its association with disease activity and exocrine gland function. Methods. The study included 295 women, 173 had a diagnosis of RA and 122 were healthy. Clinical data and blood samples were collected. Serum IL-6 levels were measured by flow cytometry, and IL-6 genotypes were performed by real-time polymerase chain reaction (PCR) using TaqMan SNP genotyping assay. Results Patients in the RA group had higher levels of IL-6 (P Conclusions The presence of the C allele of IL-6 rs1800796 plays an important role in the pathogenesis of RA and, if confirmed in other populations, may be used as a genetic marker of the disease.

Clinical Features and Genetic Polymorphism in Chinese Patients with Erythrodermic Psoriasis in a Single Dermatologic Clinic.

Erythrodermic psoriasis (EP) is a rare variant of psoriasis that involves more complications and poorer biologic drug survival than plaque-type psoriasis vulgaris (PV). No prior study has explored human leukocyte antigen (HLA) or other genetic polymorphisms in patients with EP. Our objective was to describe the clinical features, comorbidities, and HLA polymorphisms among Chinese patients with EP. We enrolled consecutive patients with EP from our clinic, with EP defined as generalized confluent erythematous thin plaques covering at least 80% body surface area. Patients were categorized as having primary or secondary EP. Aggravating factors, comorbidities including psoriatic arthritis, family history of psoriasis, age of onset, and treatment history were also identified. Genetic studies were performed for HLA-C and HLA-DRB1, and the results were compared with those from a healthy population and patients with PV. Of the 63 included patients, the male to female ratio was 2.71:1. Five (7.9%) patients had primary EP, and 58 (92.1%) had secondary EP. Genotyping of HLA-C and HLA-DRB1 was available in 61 and 58 subjects, respectively. HLA-C*0102 was the most frequent HLA-C allele (34.4%), followed by HLA-C*0702 (18.0%). The frequency of HLA-C*0602 allele (4.1%) was lower than in patients with plaque-type psoriasis (4.1 vs. 16.3%, corrected p value [Pc] = 0.02) and similar to that in the healthy population in Taiwan. The most frequent HLA-DRB1 allele was HLA-DRB1*0901 (20.7%), followed by HLA-DRB1*0803 (13.8%). An increased prevalence of psoriatic arthritis (61.9%) and higher male predominance were also noted in comparison with PV. There are HLA differences in Chinese patients with EP compared with patients with PV. The incidence of psoriatic arthritis is also higher. The implications of the above findings await further investigation.

Genetic Polymorphism in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Genetic Polymorphism in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Genetic polymorphisms in patients with type 2 diabetes mellitus and coronary heart disease

Genetic polymorphisms in patients with type 2 diabetes mellitus and coronary heart disease

Aspirin & clopidogrel non-responsiveness & its association with genetic polymorphisms in patients with myocardial infarction.

Background & objectives:Cytochrome P450, P2Y12, cyclooxygenase-1 (COX1) and glycoprotein V1 (GPVI) gene polymorphisms are known to affect patient responsiveness towards aspirin and clopidogrel dual antiplatelet therapy (DAPT). The present study was undertaken to identify aspirin and clopidogrel non-responsiveness and its association with genetic polymorphism in patients with myocardial infarction (MI).Methods:A total of 207 MI patients who were on DAPT, were included. The DAPT non-responsiveness was determined by light transmittance aggregometry using arachidonic acid and adenosine diphosphate and high platelet reactivity by collagen. Platelet activation biomarkers, thromboxane B2 (TxB2) and soluble CD40 ligand (sCD40L) were measured in plasma. Patient compliance was checked by estimating drug and its metabolite levels (aspirin and clopidogrel) in plasma using liquid chromatography-mass spectrometry/mass spectrometry. Genomic DNA was extracted, amplified by polymerase chain reaction and subsequently sequenced to identify CYP450, P2Y12, COX1 and GPVI gene polymorphisms.Results:Of the 207 patients, 32 were non-responders. The DAPT non-responsiveness was found in 15.5 per cent patients. The non-responsiveness showed a significant and an independent association with gender [odds ratio (OR)=0.18, 95% confidence interval (CI)=0.01-0.78, P=0.023], TxB2 (OR=1.00, 95% CI=1.00-1.01, P=0.013), CYP2C19*2 G>A (OR=3.33, 95% CI=1.04-10.69, P=0.044) and GPVI T>C (OR=0.23, 95% CI=0.08-0.67, P=0.007) after adjusting the demographic, clinical and genetic confounding factors when assessed between non-responder and responder compliant patients.Interpretation & conclusions:The study showed a significant association of genetic polymorphisms (CYP2C19*2 G>A and GPVI T>C) with DAPT non-responsiveness in MI patients. The findings of this study need further validation in a large cohort of patients with clinical follow up.

Vascular endothelial growth factor genetic polymorphisms at +405C/G and -460 C/T and the association with advanced stages of endometriosis

Purpose of investigation: Endometriosis is a common gynecologic disease, with a genetic component, a series of studies involving different vascular endothelial growth factor (VEGF) genetic variants in endometriosis pathogenesis. In this study, the authors aimed to describe the presence of VEGF genetic polymorphisms in relationship with endometriosis, to evaluate their relationship with VEGF serum levels, and to investigate its impact on endometriosis susceptibility. Materials and Methods: The authors studied the frequency of alleles, genotypes, and haplotypes of VEGF +405 C/G and -460 C/T genetic polymorphisms in patients with endometriosis, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: This study did not find any significant relationship between the presence of mutant allele and endometriosis. Regarding VEGF serum levels and the presence of a different allele, there was also no statistically significant difference. Conclusion: This research shows that VEGF +405 C/G and -460 C/T genetic polymorphisms are not associated with advanced endometriosis, and VEGF serum levels did not correlate significantly in relationship with the presence of a different allele and/or genotypes, thus suggesting no involvement for this polymorphism in the pathogenesis of endometriosis.

Genomic prediction of relapse in recipients of allogeneic haematopoietic stem cell transplantation

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the most informative variants while controlling against overfitting. Our results show that germline genetic polymorphisms in patients entail a significant contribution to relapse risk, as judged by the predictive performance of the model (AUC = 0.72 [95% CI: 0.63–0.81]). Furthermore, the top contributing variants were predictive in two independent replication cohorts (n = 258 and n = 125) from the same population. The results can help elucidate relapse mechanisms and suggest novel therapeutic targets. A computational genomic model could provide a step toward individualized prognostic risk assessment, particularly when accompanied by other data modalities.

POLYMORPHISM OF SOME GENES IN PATIENTS WITH CHRONIC ENDOMETRITIS

Chronic inflammation of the endometrium is one of the causes of infertility and impaired menstrual function. The issues of the diagnosis and treatment of this disease are often discussed, but remains too unclear. In connection with this, the study of the role of genetic polymorphism in patients with chronic endometritis is topical. The occurrence of polymorphisms in promoter sites of VEGF, ApoE, ESR1, PPARGC1A, MMP9, eNOS genes in patients with chronic endometritis and in practically healthy women were studied. As primers, the DNA portion of the VEGF genes rs2010963 (G634C), ApoE rs429358 (Cys130Arg), ESR1 2228480 (Thr594Thr), PPARGC1A 8192678 (Gly482Ser), MMP9 17576 (Gln279Arg), and eNOS 1799983 (Glu298Asp) were used. To study the polymorphic variants of genes investigated, a real-time polymerase chain reaction was used, the material was sampled by smear extraction from the mucous membrane of the oropharynx. In the analysis, the percentage of homozygotes and heterozygotes, the prevalence of the normal and pathological (minor) allele were counted. Based on the results obtained, it can be assumed that in patients with chronic endometritis polymorphism of genes responsible for angiogenesis, oxidative processes in the body and metabolism is more common. In particular, there was noted a statistically significant predominance of polymorphism in the promoter sites of the eNOS and ESR1 genes in patients with chronic endometritis, which may be indicative of negative genetic associations with impaired fertility; at the same time, the issues of the presence of genetic polymorphism of the genes MMP9, VEGF and ApoE and a lower frequency of somatic and gynecological pathology in a group of practically healthy women require further study.

GAPDH rs1136666 SNP indicates a high risk of Parkinson’s disease

BackgroundDevelopment of Parkinson’s disease (PD) is attributed to both genetic and environmental factors. Furthermore,GAPDH may play a key role in the development of neurodegenerative disease. Examination of genetic polymorphism in patients with sporadic PD will help uncover the mechanisms of PD pathogenesis and provide new insights into the treatment of PD. Methods and resultsThe SNaPshot method was applied to determine the gene sequences in 265 patients with idiopathic PD and 269 control cases (sex- and age-matched). The rs1136666 polymorphism of GAPDH was determined to be closely associated with PD. Subsequently, the CC genotype of the rs1136666 fragment was transfected into SH-SY5Y cells via a plasmid. The genetic expression of rs1136666 CC could induce SH-SY5Y cell injury and apoptosis via regulation of the oxidant–antioxidant and apoptosis–antiapoptosis balance. rs1136666 CC of the GAPDH had a pro-apoptotic effect similar to that of rotenone, and combination of the rs1136666 CC genetic variation and the rotenone neurotoxic effect could aggravate oxidative stress, cell injury, and apoptosis better than either single treatment alone. ConclusionThis study confirmed that the rs1136666 CC allele of theGAPDH increased the risk of PD, particularly in older male patients.

Clinical Implications of the BIM Deletion Polymorphism in Advanced Lung Adenocarcinoma Treated With Gefitinib

BackgroundProapoptotic protein Bcl-2–like 11 (BIM) is a crucial tumor suppressor gene in lung cancer development. A 2903-bp genomic deletion polymorphism is present in BIM intron 2, which alters RNA splicing and impairs the generation of the death-inducing isoform of BIM and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In the present study, we investigated the clinical implications of this genetic polymorphism in patients with advanced lung adenocarcinoma treated with gefitinib. Materials and MethodsAfter genotyping the BIM deletion polymorphism in 111 patients with stage IIIB or IV lung adenocarcinoma receiving gefitinib, the hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival and overall survival were estimated using Cox proportional hazards models. ResultsPossession of ≥ 1 deletion allele of the BIM polymorphism was observed in 18.02% of the patients. The BIM deletion polymorphism was an independent indicator of a shorter PFS (7.5 months vs. 11.3 months; HR, 2.38; 95% CI, 1.30-4.34; P = .005) and shorter OS (9.9 months vs. 27.5 months; HR, 2.53; 95% CI, 1.37-4.65; P = .003). Additionally, patients carrying the BIM deletion allele were more likely to experience acquired gefitinib-resistant disease. ConclusionOur results indicate that the BIM deletion polymorphism might be a promising germline biomarker for gefitinib treatment in Chinese patients with lung adenocarcinoma.