Impact Of Genetic Factors Research Articles

Monocytes/macrophages karyologic indices in patients with chronic heart failure

Genetic factors impact in chronic heart failure (HF) development is discussed during last decades. The aim was to evaluate cytogenetic status of patients with ischemic HF with karyologic analyzes of monocytes/macrophages. Methods and results. 24 patients and 12 practically healthy persons (control group) were included into the study. Internuclear bridges, perinulcear vacuolization, vacuolization and nuclear chromatin condensation were detected more frequent in patients with HF than in control. Conclusion. This indicates proliferation activation and is initial signs of apoptosis/necrosis in observed cells.

In 250 Children, Is Wolly Genetic the Transmission of Allergy and Asthma I, Mainly If these Children are Asthmatic?

There seems to be no unanimity of opinion as to the mode of transmission of allergic disease. According to some, allergy is transmitted as a simple Mendelian dominant. In direct contrast, others maintain that the findings favor a recessive mechanism. Further- more, others suggest that the condition is inherited as a “partial dominant” disorder. An additional analysis of family studies as well as data already published, failed to support either the simple dominant or recessive theory. The dominant theory does not explain why in more than half of the pedigrees both parents are normal. The recessive theory is refuted by the existence of pedigrees in which both parents are affected, yet some of the children are normal. To put more order in this complex mess, we have decided to study the genetic risk of children with a family history (FH) of allergy, We have therefore formed this prospective study in 250 children that included: family (FH) and personal history, skin prick tests (SPTs) and specific IgE (RAST), who were admitted to the Pediatric Allergy and Immunology Division of Rome University since they were affected with respiratory allergy. We have prepared a sheet with questions and possible answers. Consequently, we have studied the FH of these children asking whether their parents and brothers/sisters had atopic diseases, and specifying whether such disorders were respiratory or food allergies (FA). The parents of all children gave their informed consent. We analyzed data using the X2 method. 42.3% of their parents were atopic, as well as their 20 brothers/sisters. In total, 90.2% of fathers, 84% of mothers and 65% of brothers/ sisters had asthma or allergic rhinitis (AR). We add that some parents had urticarial, further there were mothers and brothers/sisters experiencing atopic dermatitis (AD), and some mothers with food allergy (FA). In 23 children from these parents most had AD and respiratory allergy. In 250 children comparable for age and sex with no respiratory disorder supplied from our outpatient clinic 40 parents, 14 mothers and 26 fathers and 9 brothers/sisters had asthma or AR (p = 0.0001), some fathers had also urticaria and two brothers AD. A major part of respiratory allergy is not transmitted by mothers: we stress that 42.3% of parents are atopic, and FH of their children was positive for respiratory allergy in 82-92% of cases. Thus respiratory allergy can have an autosomal dominant mode of inheritance, but considering the other atopic diseases, the transmission can be polygenic. The impact of genetic factors in these children is stressed by the relevant quote of asthmatic brothers/sisters.

Frequency of CYP2C9 and VKORC1 gene polymorphisms and their influence on warfarin dose in Egyptian pediatric patients.

Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. CYP2C9 (*2 and *3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. The allele frequency of the studied genes was CYP2C9*2 (0.085), CYP2C9*3 (0.12), VKORC1 1173T (0.52), and VKORC1 -1639A (0.54). In univariate analysis, patients' age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.

What is the ethnicity-specific impact of genetic polymorphisms on the response to hepatitis C treatment in an admixed population of Brazilian patients?

Dear Editors, We read with great interest the article by Angelo et al. in CLINICS 1. This study revealed interesting points regarding the impact of different genetic polymorphisms on hepatitis C treatment efficacy in 181 Brazilian patients. The evaluation of multiple genetic polymorphisms in this study encouraged us to appreciate the authors' attempt to show the impact of host genetics on the treatment response in hepatitis C virus (HCV)-infected Brazilian patients of admixed ethnicity. Although the statistical analysis in this study was comprehensive in its assessment of the association between different genetic polymorphisms and treatment response, we have several concerns about this statistical analysis. We believe that the frequencies of the polymorphism genotypes should have been reported for the response groups instead of the polymorphisms genotypes that were reported throughout the article. As a result, the presentation of the frequencies of the polymorphism genotypes in Table 2 would be preferable in vertical order instead of in horizontal order 2. Additionally, the protective genotype frequencies in the sustained virological response group, which were presented in the abstract, should be considered in the following manner: 44.2% rs4969170 G/G; 17.3% rs2853744 T/T; 69.2% rs11730582 T/T; 76.9% rs2071430 G/T; and 45.5% rs12979860 C/C. On the other hand, data on the rs12979860 genotype were included for 139 individuals in Table 2, and it appeared that the data on the rs12979860 genotyping was missing for 42 patients in this study. The authors reported that the frequency of rs12979860 C/C was 18.8% in the study population, which seems to be incorrect; considering the missing data in the statistical calculation, we found the rs12979860 C/C genotype frequency to be 24.5%. Another point that we would like to address in this letter is that a multivariate analysis should have been considered by the authors to clarify the adjusted impact of each polymorphism alongside other factors, such as liver fibrosis, on the response to hepatitis C treatment 3. Finally, because the impact of genetic factors on the HCV treatment response in populations with admixed ethnicity has been not well studied, a study on a large sample of different ethnicities in regions with an admixed population, such as Brazil, is highly recommended. Each genetic marker could have an ethnicity-specific influence on the response to hepatitis C treatment, which should be investigated in a population-based setting.

Can Genetics Help in Treatment of Smoking Addiction?

Although the harmful health effects of smoking are well-known, roughly fifth of mankind is still smoking. Because quitting smoking is difficult mainly due to the addictive effect of nicotine, several attempts have been made to ease this in the smoking cessation process. These attempts have been complicated by existence of a substantial variability in the nicotine addiction and relapse times, shown to be attributable to both environmental and genetic factors. The new emerging means like personalized medicine are hoped to help in overcoming the obstacles caused by the inherited factors in the treatment of tobacco dependence. The personalized treatment of smokers would be cost-effective, safe from gratuitous medicine taking and would improve the success rate of long term abstinence, which all can be enabled by the means of genetic studies. The impact of genetic factors on individual response to smoking cessation treatments has therefore been of great interest during the recent years. The focus of these studies has been on relationship between candidate gene polymorphisms and individual differences in smoking behavior and ability to quit smoking, especially considering the impact of multiple genetic variants of some smoking-related pathway on both nicotine dependence and individual response to smoking cessation treatments. This expert review summarizes the present knowledge on the genetic factors in smoking addiction and the potential of this knowledge to advance the future smoking cessation actions.

O-25 PGD for monogenic disorders on polar bodies and trophectoderm biopsies – potential impact of genetic factors and hormone treatment on the outcome of polar body diagnosis, “PBD”

O-25 PGD for monogenic disorders on polar bodies and trophectoderm biopsies – potential impact of genetic factors and hormone treatment on the outcome of polar body diagnosis, “PBD”

Impact of genetic factors on dyslipidemia in HIV-infected patients starting antiretroviral therapy

The impact of host genetic factors on the incidence of dyslipidemia in antiretroviral-naive HIV patients starting antiretroviral therapy (ART) is not clear. We assessed the role of single nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies adjusting for the contribution of nongenetic factors. We assessed 192 SNPs in an HIV cohort who started ART (1997-2008) including a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (NNRTI). Patients had fasting plasma lipids, total cholesterol (T-Chol), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides measured prior to their ART initiation and after 1 year. A logistic regression model was constructed and multiple test was corrected using 10% false discovery rate (FDR). Haplotypes and gene interactions were analysed. A total of 727 individuals were successfully genotyped (n = 381_PI-group; n = 346_NNRTI-group). Age and hepatitis C virus (HCV) coinfection were associated with increases and decreases in T-Chol and LDL-C (P < 0.01), respectively. Protease inhibitor containing ART showed an unfavourable association with T-Chol (P < 0.01) and triglycerides (P = 7.4E-4) and NNRTI-containing ART was favourably associated with HDL-C (P < 0.01). Moreover, SNPs in apolipoprotein B (APOB) were associated with an increase of LDL-C [rs10495712 (P = 3.18E-4); rs754524 (P = 1.26E-3)]. Six SNPs in three genes showed an association with a favourable effect on HDL-C levels when ART included NNRTI: ABCA1 (rs4149313, P = 2.97E-4), LIPC (rs1800588, P = 2.13E-3; rs473224, P = 3.06E-4; rs261336, P = 2.23E-3) and CETP (rs173539, P = 2.96E-3; rs3764261, P = 1.52E-3). After 10% FDR correction for multiple testing, one and six SNPs displayed significant associations with LDL-C and HDL-C, respectively. In HIV-infected patients staring ART, one SNP in APOB was associated with an increase of LDL-C. SNPs in ABCA1/LIPC/CETP were favourably associated with HDL-C when ART included NNRTI. However, an unfavourable effect on T-Chol and triglyceride levels was observed when ART included protease inhibitor. The risk of hypercholesterolaemia increased with age and decreased with HCV coinfection. These findings might help to individualize the selection of ART.

Functional stress response in patients with rheumatoid arthritis: Impact of genetic factors

It is still incompletely understood how the stress response contributes to the pathogenesis of rheumatoid arthritis (RA). To characterize neuroimmune interactions, common variants in the genes of the β2-adrenergic receptor (beta2AR) and corticotropin releasing hormone (CRH) were studied together with functional stress responses in RA patients. An allele-specific PCR was used to determine the polymorphisms of the beta2AR (position 16, 27, 164), as well as the polymorphic sequences in the 5′ flanking region of the human CRH gene in RA patients (n = 310) and controls (n = 305). The autonomic response upon stressful stimuli was investigated studying heart rate variability, and the dynamics of blood glucose levels, CRH, and cortisol production under insulin hypoglycemia (IHT). There was a highly significant distortion in the distribution of the beta2AR polymorphism at codon 16 between RA patients and controls (p = 0.00001). It was also revealed a significant decrease of parasympathetic activity in patients with homozygosity for Gly 16 compared to Arg16Gly RA patients. In addition, the CRH promoter polymorphisms exerted a significant influence on the stress response of RA patients undergoing IHT. The integrated cortisol response to hypoglycemia was significantly lower in RA patients bearing the A1B1 allele compared to the A2B2 (p = 0.016). Polymorphisms of the beta2AR and CRH are associated with disturbed functional stress reactivity on various levels in RA patients. Further studies are warranted to determine the role of genetic factors on stress response in the disease process of RA.

IL-17 Gene Polymorphism Is Associated with Chronic Periodontitis and Peri-implantitis in Iranian Patients: A Cross-Sectional Study

Periodontal disease (PD) and peri-implantitis (PI) are characterized by an immune response leading to destructive inflammation. The prominent impact of genetic factors on periodontitis has been previously evaluated and IL-17 has found to play a critical role in this process. This cytokine has a controversial behavior. This study aimed at finding out whether the polymorphism of this cytokine plays a significant role in chronic periodontitis (CP) and PI or it is just a pro-inflammatory regulatory cytokine. Fresh human blood samples were obtained and three main genotypes were traced carefully. The samples were transferred into 96-well plates and sent to KBioscience Institute in the United Kingdom for genotyping the polymorphism using Competitive Allele Specific PCR (KASP) technique. SPSS version19 software and chi-square and Kruskal–Wallis tests were used for statistical differences considering p-value less than 0.05. A significant difference was detected between the three groups in terms of specific SNP studied in this experiment (P = 0.00). The CC genotype of IL17 polymorphism (rs10484879) may contribute to the pathogenesis of peri-implantitis and periodontitis. The association of IL-17 polymorphism with PI and CP is a promising finding that may help in future similar studies on other ethnicities and larger study populations.

Genetic variation of the natural killer gene complex has a role in lung cancer susceptibility.

Worldwide estimates indicate lung cancer is the leading cause of death among all cancers, while also being the most frequently diagnosed of new cancer cases (1). Non-small cell lung carcinoma is the most frequent subtype. Exposure to environmental carcinogens, such as radon and tobacco inhalation, is a major risk factor for developing lung cancer. Familial heredity also increases an individual’s risk, although the impact of genetic factors on the development of lung cancer remains unclear, especially within the context of immune response. Innate and adaptive immune systems may inhibit or enhance carcinogenesis depending on the recruitment of specific immunocompetent cells (2).

Biological pathways and genetic mechanisms involved in social functioning

To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

Impact of genetic factors (VKORC1, CYP2C9, CYP4F2 and EPHX1) on the anticoagulation response to fluindione

Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9) and of a key pharmacologic target of vitamin K antagonists, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to coumarin derivatives. The role of these variants in fluindione response is unknown. Our aim was to assess whether genetic factors contribute to the variability in the response to fluindione. Four hundred sixty-five patients with a venous thromboembolic event treated by fluindione for at least 3 months with a target international normalized ratio (INR) of 2.0 to 3.0 were studied. VKORC1, CYP2C9, CYP4F2 and EPHX1 genotypes were assessed. INR checks, fluindione doses and bleeding events were collected. VKORC1 genotype had a significant impact on early anticoagulation (INR value ≥2 after the first two intakes) (P < 0.0001), on the time required to reach a first INR within the therapeutic range (P < 0.0001) and on the time to obtain a first INR value > 4 (P= 0.0002). The average daily dose of fluindione during the first period of stability was significantly associated with the VKORC1 genotype: 19.8 mg (±5.5) for VKORC1 CC, 14.7mg (±6.2) for VKORC1 CT and 8.2mg (±2.5) for VKORC1 TT (P < 0.0001). CYP2C9, CYP4F2 and EPHX1 genotypes did not significantly influence the response to fluindione. VKORC1 genotype strongly affected anticoagulation induced by fluindione whereas CYP2C9, CYP4F2 and EPHX1 genotypes seemed less determining.

Incidence of pancreatic cancer in Greenland 2000–2010

Background. Inuit people are known to be at an increased risk of cancers usually uncommon to the western world such as cancers of the nasopharynx and salivary glands. But what is the trend regarding pancreatic cancer?Objective. To determine the incidence of pancreatic cancer (PC) in Greenland compared with Denmark in the period 2000–2010.Study design. Retrospective register-based study. Cases were retrieved from The Danish Cancer Register and The Greenlandic Patient Register and stratified in 5-year age intervals for each year. Age-standardized incidence ratios (SIR) for each year for Greenland compared with Denmark were calculated using the number of cases and the number of inhabitants in each 5-year age interval and in each country. The average SIR for the entire period was calculated using a weighted average.Results. The study revealed a SIR of 2.38 (95% CI: 1.97–2.86; p<0.0001) indicating a significantly increased incidence of PC in Greenland compared with Denmark. A linear regression analysis showed no significant change in the SIR over time (p for trend 0.25) as well as no significant change isolated in Greenland (p for trend 0.8). Furthermore, the Inuit were significantly younger at the time of diagnosis (mean 62.7 vs. 70.0; p<0.0001).Conclusions. The age-standardized incidence of PC is 138% higher in Greenland than in Denmark. A part of this could be explained by a higher prevalence of smoking and DM-2. However, the impact of genetic factors cannot be disregarded and should be subjected to further investigation.

Thr92Ala Polymorphism of Human Type 2 Deiodinase Gene (hD2) Affects the Development of Graves' Disease, Treatment Efficiency, and Rate of Remission

Clinical symptoms vary in thyrotoxicosis, and severity of these depends on many factors. Over the last years, impact of genetic factors upon the development and clinical significance of thyrotoxic symptoms became evident. It is known that a production of T3 in various tissues is limited by deiodinase 2 (D2). Recent studies revealed that certain single nucleotide polymorphisms (including threonine (Thr) to alanine (Ala) replacement in D2 gene codon 92, D2 Thr92Ala) affect T3 levels in tissues and in serum. Individuals with Ala92Ala genotype have lower D2 activity in tissues, compared with that in individuals with other genotypes. In our study, we have assessed an association of D2 Thr92Ala polymorphism with (1) frequency of disease development, (2) severity of clinical symptoms of thyrotoxicosis, and (3) rate of remissions, in Graves' disease patients.

Brain Plasticity and Genetic Factors

Brain plasticity refers to changes in brain function and structure that arise in a number of contexts. One area in which brain plasticity is of considerable interest is recovery from stroke, both spontaneous and treatment-induced. A number of factors influence these poststroke brain events. The current review considers the impact of genetic factors. Polymorphisms in the human genes coding for brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) have been studied in the context of plasticity and/or stroke recovery and are discussed here in detail. Several other genetic polymorphisms are indirectly involved in stroke recovery through their modulating influences on processes such as depression and pharmacotherapy effects. Finally, new genetic polymorphisms that have not been studied in the context of stroke are proposed as new directions for study. A better understanding of genetic influences on recovery and response to therapy might allow improved treatment after stroke.

The impact of genetic factors in the development of thrombosis in cancer patients

e22227 Background: Thromboembolism is frequent in patients with cancer. Although it is known that several acquired factors take place in this process, the role of the genetic factors is controversial. In this study we analysed the most common genetic polymorphisms which have a role in the development of thrombosis. Methods: Study population consists of 292 (158 with thrombosis and 134 without thrombosis) patients treated between 2004 and 2008. Thrombosis was diagnosed by clinically and radiological measures in any time during the course of disease. Factor V Leiden G1691A, Prothrombin G20210A, Methlene Tetra Hydrofolate Reductase (MTHFR) C677T and Plazminogen Activator Inhibitor (PAI-1) 4G/5G were analysed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Results: In the study group 48 and 1 patient had heterozygot and homozygot polymorphism for Factor V Leiden G1691A respectively. In the control group 32 heterozygot and 1 homozygot polymorphism and there was no statistically significant differents between study and control group (p=0,462).For Protrombin G20210A 11 and 4 heterozygot polymorphism were observed in control and study group respectively. While there was 1 homozygot polymorphism in study group there was no in control group and the difference between two groups was not statistically significant (p=0,198). For MTHFR C677T, 48 and 24 heterozygot polymorphism, 15 and 12 homozygot polymorphism were observed in study and control group respectively. The difference between two groups were statistically significant (p=0,04). There was no statistically significant difference between two groups for PAI-1 4G/5G polymorphisms (p=0,362). In subgroup analyses, statistically significant difference was found only in MTHFR C677T polymorphism in patients with GI cancer and with and without thrombosis (p=0,028). Conclusions: The studies investigating the relationship between genetic factors and thrombosis revealed controversial results. However, we found no genetic factor relevant to thrombosis other than MTHFR C677T polymorphism. Further studies investigating genetic and acquired factors in the development of the thrombosis in detail are warranted for documenting clearly the role of genetic polymorphisms. No significant financial relationships to disclose.

Correlation trends for bone mineral density in Mexican women: evidence of familiar predisposition

Genetic factors determine bone mineral density (BMD) and peak bone density between 20 and 30 years of age, as well as bone mineral loss after menopause. BMD is a predictor of fractures due to osteoporosis and the impact of genetic factors on osteoporosis. The variation in BMD for each individual is determined by an underlying genetic structure, common genetic effects, particularly with respect to compact bones as compared to those that are primarily trabecular. This article presents the correlation of BMD by anatomical site among different samples of Mexican grandmothers, mothers and granddaughters of mixed race. The present analysis was performed of healthy employees and their healthy relatives from three different health and academic institutions: the Instituto Mexicano del Seguro Social and the Instituto Nacional de Salud Pública, both located in Cuernavaca, Morelos, as well as the Universidad Autónoma del Estado de México. We selected family-related female participants in order to obtain pairs of mothers and daughters and, whenever possible, grandmother-mother-daughter groups. We were able to match 591 mother-daughter pairs for analysis. Additionally, we were able to include grandmothers to create grandmother-mother-daughter triads for further analysis. Bone density measurements were performed of the non-dominant proximal femur, the lumbar spine (L1-L4) and the whole body using a dual X-ray absorptiometry (DXA) Lunar DPX NT instrument. This study included 591 granddaughters, 591 mothers and 69 grandmothers; mean ages were 20, 47 and 72 years old, respectively. A close relationship existed with respect to body mass index (BMI) between mothers and grandmothers (27.9 vs. 27.3). The largest proportion of body fat mass was observed in the group of mothers (28.5%), but was also high in grandmothers (25.7%) and granddaughters (21.1%). The percentage of lean body mass was similar among the three family groups. The correlation of BMD between mothers and grandmothers was greatest for subtotal BMD (0.44) and was very high for the hips (0.39). Using predictive models for hip BMD among grandmothers, mothers and grandchildren, we observed that hip BMD of grandmothers is a predictor of BMD in mothers, with a beta of 0.46 (p 0.001, CI95% 0.19-0.73); (R(2): 0.41). A predictor of BMD of the lumbar spine in grandchildren is BMD of the lumbar spine in mothers (beta 0.30 CI95% 0.07-0.53). The results obtained in this study suggest that daughters whose mothers have a low BMD for their age will tend to develop the same condition. This indicates the importance of monitoring for girls and adolescent females whose mothers have problems related to osteopenia or osteoporosis. It will therefore be necessary to conduct studies to identify the most significant genes and specific anatomical sites among our population for the purpose of establishing the polymorphic variants for high-risk in the Mexican population.

Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma

The impact of genetic factors on asthma is well recognized but poorly understood. We tested the hypothesis that different mouse strains present different lung tissue strip mechanics in a model of chronic allergic asthma and that these mechanical differences may be potentially related to changes of extracellular matrix composition and/or contractile elements in lung parenchyma. Oscillatory mechanics were analysed before and after acetylcholine (ACh) in C57BL/10, BALB/c, and A/J mice, subjected or not to ovalbumin sensitization and challenge. In controls, tissue elastance (E) and resistance (R), collagen and elastic fibres' content, and alpha-actin were higher in A/J compared to BALB/c mice, which, in turn, were more elevated than in C57BL/10. A similar response pattern was observed in ovalbumin-challenged animals irrespective of mouse strain. E and R augmented more in ovalbumin-challenged A/J [E: 22%, R: 18%] than C57BL/10 mice [E: 9.4%, R: 11%] after ACh In conclusion, lung parenchyma remodelled differently yielding distinct in vitro mechanics according to mouse strain.

Role of genetic factors in extinction of island endemics: complementary or competing explanations?

Role of genetic factors in extinction of island endemics: complementary or competing explanations?

Genetic Factors in Outcome After Traumatic Brain Injury

It is becoming increasingly clear that genetic factors modify outcome after traumatic brain injury (TBI). The best known example of this is the association between the apolipoprotein E4 allele (APOE epsilon4) and poorer outcomes. However, our knowledge of the many other genes that might influence outcome is still in its infancy. This article will review the basic principles underlying recent advances in genetics, and then describe the current state of knowledge regarding the impact of genetic factors on TBI outcome. We conclude that although genetic advances have implications for prognosis, their biggest contribution will be to elucidate the pathophysiology of TBI, potentially leading to new treatments.