Research Progress on Genetic Susceptibility to Triple-Negative Breast Cancer / 肿瘤防治研究

Triple-negative breast cancer (TNBC) is a type of breast cancer that is difficult to treat, has a poor prognosis, and is prone to recurrence and metastasis in the early postoperative period. The age of patients is tending younger, and the racial difference is large. It is also related to family history, and genetic susceptibility is obvious. So, elucidating the genetic risk factors of TNBC and obtaining precise therapeutic targets are urgent tasks. Obtaining reliable characteristic genes and their polymorphisms between TNBC of different subtypes is difficult. This review summarizes the susceptibility genes and the polymorphisms of TNBC susceptibility genes of different molecular subtypes, in order to develop effective TNBC prevention strategies and find effective therapeutic targets. This review provides a theoretical basis for promoting the study of TNBC from the perspective of genetics.

Genetic susceptibility genes and clinical features of early-onset breast cancer / 国际肿瘤学杂志

Objective:To explore the germline mutation frequency of genetic susceptibility genes and clinical characteristics in early-onset breast cancer (onset age ≤35 years) in China.Methods:Clinical information and peripheral blood of 150 patients aged 35 and younger diagnosed with breast cancer in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to December 31, 2019 were collected. Then DNA was extracted to detect germline mutations in breast cancer susceptibility gene (BRCA) 1, BRCA2, ataxia telangiectasia mutated (ATM) , partner and localizer of BRCA2 (PALB2) , tumor protein 53 (TP53) and cell cycle checkpoint kinase 2 (CHEK2) genes. Mutations were interpreted as pathogenic, likely pathogenic, uncertain significance, likely benign and benign according to the classification criteria and guidelines for genetic variation. Patients were divided into mutation group ( n=18) and non-mutation group ( n=132) according to the presence or absence of pathogenic or probable pathogenic germline mutations, and the χ2 test was used to analyze the relationships between genetic susceptibility gene mutations and clinicopathological characteristics. Results:Eighteen pathogenic or likely pathogenic germline mutations were detected in 150 patients with early-onset breast cancer, for an overall mutation frequency of 12.0%. Among them, there were 8 (5.3%) BRCA2 mutation, 7 (4.7%) BRCA1 mutation, 1 (0.7%) PALB2 mutation, and 2 (1.3%) TP53 mutation. There were no pathogenic or likely pathogenic variants in ATM and CHEK2 genes. The mutation type was dominated by frameshift mutation (9/18, 50.0%) , followed by nonsense mutation (7/18, 38.9%) , missense mutation (1/18, 5.6%) and splice acceptor mutation (1/18, 5.6%) . Among the molecular subtypes of 18 mutation carriers, 9 cases were Luminal B, 6 cases were triple negative breast cancer (TNBC) , 2 cases were Luminal A, and only 1 case was human epidermal growth factor receptor-2 (HER-2) amplification. Among them, 8 BRCA2 mutation carriers were Luminal type, and 6 of 7 BRCA1 mutation carriers were TNBC type. There were no statistical differences in family history of breast cancer ( P=0.343) , estrogen receptor (ER) status ( χ2=0.16, P=0.688) , HER-2 status ( χ2=2.89, P=0.089) , molecular subtype ( χ2=1.99, P=0.575) , and initial diagnosis TNM stage ( χ2=2.49, P=0.115) between the mutation group and the non-mutation group. Conclusion:The patients with early-onset breast cancer have high frequency of germline mutations. It is recommended that patients with early-onset breast cancer undergo genetic counseling and multigene testing.

Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population

BACKGROUND: Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families. METHODS: The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay. RESULTS: Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0-1.6] p = 0.02 and OR = 1.5 [95% CI 1.0-2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0-1.7] p = 0.02 and OR = 1.3 [95% CI 1.0-1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0-3.1] p = 0.03 and OR = 1.9 [95% CI 1.1-3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002). CONCLUSIONS: Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.

Research progress in genetic susceptibility genes and related pathogenic factors and treatment of neoplastic calcinosis / 国际生物医学工程杂志

Tumor calcinosis(TC) has different clinical and biochemical patterns. The existence of chronic injury as well as calcium and phosphorus metabolism disorder has been gradually proved to be the important link in the occurrence of TC. In this paper, the related basic diseases with the pathophysiological mechanism of calcium and phosphorus metabolism disorder were reviewed, and the pathophysiological mechanism of phosphate metabolism disorder in various diseases was summarized.In addition, the phosphate homeostasis genes including GALNT-3, FGF-23 and α-KLOTHO were described. The relevant research results have showed that mutations in any of these three genes will lead to defects in the synthesis or action of FGF-23, which will increase the reabsorption of phosphate by renal tubules, resulting in hyperphosphatemia and severe ectopic calcification of soft tissue.At present, surgical resection is still the main treatment of TC. New technologies such as cinalcet peritoneal dialysis, ultrasound-guided aspiration of TC lesions and local injection of sodium thiosulfate (STS), as well as the successful application of lanthanum carbonate and other drugs, provide alternatives to TC treatment.In this paper, the research literatures on TC at home and abroad in recent years were introduced and the genetic susceptibility genes, related pathogenic factors and the latest treatment progress of TC were reviewed.

Molecular pathologic mechanism associated with ischemic optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Nonarteritic anterior ischemic optic neuropathy(NAION)is caused by ischemia of the short posterior ciliary artery that supplies the lamina area of the optic disc. It usually occurs in over 50-year-old people. It is acute optic neuropathy and featured with acute, monocular, and painless vision loss, which frequently results in severe permanent vision damage and visual field defects. This disease is attracting increased attention of clinical researchers. This paper overviews the current molecular pathology of NAION from these aspects, including pathogenesis, pathological changes, relevant protein molecules and susceptibility genes in previous studies. This paper lays a theoretical foundation for future research on the pathological mechanism and the treatment of NAION.

Associations among Genetic Variants and Intracranial Aneurysm in a Chinese Population

PURPOSE: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17, RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. MATERIALS AND METHODS: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. RESULTS: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA, SOX17, or RBBP8 and IA. CONCLUSION: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.

Genetic Study of Inflammatory Bowel Disease and its Clinical Application / 胃肠病学

Inflammatory bowel disease (IBD) is an idiopathic and chronic non-specific inflammatory disease of gastrointestinal tract. Abnormal immune response in intestinal mucosa toward commensal microbiota together with intestinal mucosal barrier defects, genetic and environmental factors might be associated with the pathogenesis of human IBD. In recent years, great progress has been made in genetic study of IBD, providing important help for clinical translation and application. Genetic analysis will help us to explain the etiology and lesional areas of IBD, predict the disease behaviors and effectiveness of treatment, thereby benefits the clinical diagnosis and treatment of the disease. This review summarizes the latest achievements and new progresses in genetic study and clarifies the potential value of genetic study in management of IBD.

Research advances on the TCA cycle in pheochromocytoma and paraganglioma / 中华内分泌代谢杂志

In pheochromocytoma and paraganglioma (PPGL), mutations in the TCA cycle related genes may lead to the disturbance of the TCA cycle's intermediate metabolite levels, then cause pseudohypoxia by abnormal hypoxia-inducible factor ( HIF) activation, it also may lead to epigenetic changes, impede cell differentiation and apoptosis, and finally promote the occurrence and development of PPGL. This review focus on the research advances on the TCA cycle in the pathogenesis of PPGL, as well as the application of relevant detection methods.

Research advances in susceptibility genes of non-alcoholic fatty liver disease and its association with type 2 diabetes / 中国药科大学学报

@#Nonalcoholic fatty liver disease(NAFLD)as the most common hepatic disease worldwide is affected not only by extrinsic factors, but also by genetic ones. Type 2 diabetes mellitus(T2DM), another chronic disease regulated by both environmental and genetic factors, is closely related to NAFLD in signal pathways and susceptibility genes. This review summarizes the susceptibility genes of NAFLD, especially points out their relevance to T2DM and suggests their related clinical applications, which provide further evidence for the exploration of the mechanisms of the two diseases with a new direction for their diagnosis and treatment.

The study progress of common susceptibility genes of breast cancer / 中华内分泌外科杂志

Breast cancer is a common malignancy for women.Since 21st century,the incidence of breast cancer has been increasing all over the world and ranked first among all the female malignancies in the developed regions of Europe and America.With the increase of the morbidity of breast cancer,experts have paid more and more attention to the study of the susceptibility genes of breast cancer.The research of breast cancer susceptibility genes will help to understand the causes of breast cancer,find out available preventive measures,diagnose and treat patients with breast cancer in the early period.Specially,susceptibility genes also play an important role in the screening,early diagnosis and preventive treatment for those with family history of breast cancer or the carriers of the susceptibility genes mutation.The susceptibility genes of breast cancer include the high-penetrance susceptibility genes,the moderate-penetrance susceptibility genes,and the low-penetrance susceptibility genes.Nowadays,there are plenty of studies of BRCA1 and BRCA2,two of the high-penetrance susceptibility genes of breast cancer.The review summarizes the current study progress of the common susceptibility genes of breast cancer.

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate- and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

Progress of the susceptibility genetic research on asthma / 国际儿科学杂志

Bronchial asthma is a complex polygenic disease,caused by environmental and genetic factors.Three key methods are used to identify asthma susceptibility genes,including positional cloning study,candidate gene study and the emerging trend of genome-wide association study.Chain analysis and correlation analysis are two main strategies.This review discusses the asthma susceptibility genes:TLR,IL-13,PDCD4,CCL-5,TRPV1,BDNF in the perspective of functional classification.

Research Progress of the Correlation between Phlegm Syndrome and Susceptibility Genes in Metabolic Syndrome / 中国中医药信息杂志

Metabolic syndrome (MS) is a complex polygenic inheritance disease, caused by the accumulative effect of multiple genes and some environmental factors. Insulin resistance is the pathophysiologic foundation of MS. From the viewpoint of TCM, phlegm is the basic pathological factor of MS. In different periods and different symptoms of the disease, phlegm can be found during the whole disease course. Genes as an important component of the innate factors, play an important role in the formation of phlegm syndrome. Researches on correlation between susceptibility genes and phlegm syndrome in MS are important to enrich the connotation of phlegm syndrome and improve the level of diagnosis and treatment for this disease.

A research on relationship between single nucleotide polymorphism of susceptibility genes of type 2 diabetes mellitus and gestational diabetes mellitus / 国际检验医学杂志

Objective To investigate the relationship between single nucleotide polymorphism (SNP) of susceptibility genes CD-KAL1 ,CDKN2A-CDKN2B ,TCF7L2 and HHEX-IDE of type 2 diabetes mellitus and gestational diabetes mellitus (GDM) in Jiangsu region .Methods 185 healthy pregnant women without GDM tendency (control group) and 176 pregnant women with GDM (GDM group) were enrolled .Case-control method and Multiplex SNaPshot SNP genotyping technology were utilized to detect genotypes at SNP loci of CDKAL1 ,CDKN2A-CDKN2B ,TCF7L2 and HHEX-IDE of pregnant women both in the two groups , and all SNP loci were subject to continuous disequilibrium analysis .Results Compared the allele frequencies of pregnant women in GDM group and the control group ,C allele of CDKAL1(rs7754840) was a risk factor for GDM .The risk of suffering GDM of CC genotype carriers was 1 .73 times the non-CC genotype carriers[P<0 .01 ,OR=1 .73 ,95% CI:1 .28-2 .33] .No statistical difference wasfound in gene distribution of detection loci of CDKN2A-CDKN2B(rs10811661),TCF7L2(rs7903146) and HHEX-IDE (rs1111875) .The genotype frequencies of CDKAL1(rs7754840) ,CDKN2A-CDKN2B(rs10811661) ,TCF7L2(rs7903146) and H HEX-IDE(rs1111875) were all accordance with the law of genetic equilibrium .Conclusion CDKAL1(rs7754840) is closely re-lated to GDM susceptibility in Jiangsu region .

Advances in Studies on Serum Biomarkers and Susceptibility Genes in Differential Diagnosis of Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease (IBD)includes Crohn’s disease (CD)and ulcerative colitis (UC).The differential diagnosis between CD and UC mainly depends on clinical symptoms,endoscopy,pathological biopsy,laboratory and imaging examinations.In recent years,studies with a variety of IBD-related biomarkers develop rapidly because of its non-invasiveness,simple and easily acceptable.With the development of genome-wide association study (GWAS),great progress has been achieved in studies of gene mutations and susceptibility genes related with CD and UC,which provides new approach for diagnosis of the disease.This article reviewed the advances in studies on serum biomarkers and susceptibility genes in differential diagnosis of IBD.

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Progress of the genetic research on asthma / 国际儿科学杂志

Bronchial asthma is a chronic inflammatory disorder of the airways,caused by multiple genetic and environmental factors.Thtee key methods including candidate gene study,the positional cloning and genomewide association studies.are used for asthma susceptibility gene identification.There are many candidate genes that haye been identified as asthma susceptibility gene, including ADRB2,IL4R,FLG,NPPA,INPP4A,ADAM33, DPP10,OPN3,0RMDL3,PDE4D,CHBLI etc.Replication of genetic associations and demonstration of a functional mechanism for the associated gene variants are needed to COnfirm an asthmasusceptibility gene, this will help us to understand the aetiology of asthma and explore new drugs to treat asthma.

Genetics of homocysteine metabolism and associated disorders

Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, an essential amino acid, and is metabolized by one of two pathways: remethylation or transsulfuration. Abnormalities of these pathways lead to hyperhomocysteinemia. Hyperhomocysteinemia is observed in approximately 5 percent of the general population and is associated with an increased risk for many disorders, including vascular and neurodegenerative diseases, autoimmune disorders, birth defects, diabetes, renal disease, osteoporosis, neuropsychiatric disorders, and cancer. We review here the correlation between homocysteine metabolism and the disorders described above with genetic variants on genes coding for enzymes of homocysteine metabolism relevant to clinical practice, especially common variants of the MTHFR gene, 677C>T and 1298A>C. We also discuss the management of hyperhomocysteinemia with folic acid supplementation and fortification of folic acid and the impact of a decrease in the prevalence of congenital anomalies and a decline in the incidence of stroke mortality.

Patogênese das doenças tiroidianas autoimunes / Pathogenesis of autoimmune thyroid diseases

A doença tiroidiana autoimune (DAIT), que afeta de 2 por cento a 5 por cento da população ocidental, é o transtorno autoimune órgão-específico mais comum. Sua apresentação clínica varia do hipertiroidismo da doença de Graves (DG) ao hipotiroidismo associado à tiroidite de Hashimoto (TH). A exata etiologia da DAIT permanece desconhecida, mas a interação entre suscetibilidade genética e fatores ambientais desencadeadores parece ser de fundamental importância no seu desenvolvimento. Postula-se que fatores genéticos responderiam por 79 por cento da suscetibilidade à DAIT e os ambientais por 21 por cento. Genes imunomoduladores, como o complexo maior de histocompatibilidade (MHC), antígeno-4 associado ao linfócito T citotóxico (CTLA-4), a molécula CD40 e a proteína tirosina fosfatase-22 (PTPN22) e os genes específicos da glândula tiróide, como receptor do TSH (TSHR) e tiroglobulina (TG) têm sido identificados. A natureza exata do envolvimento do meio ambiente no desenvolvimento da DAIT não é bem conhecida, mas vários fatores ambientais têm sido envolvidos, como o conteúdo de iodo na dieta, estresse, drogas e infecções. Entretanto, não há evidência clara de causalidade e os mecanismos pelos quais fatores ambientais desencadeariam a autoimunidade tiroidiana, em indivíduos geneticamente predispostos, ainda permanecem não completamente entendidos. O conhecimento dos mecanismos precisos de interação entre fatores ambientais e genes na indução da autoimunidade tiroidiana poderia resultar desenvolvimento de novas estratégias de prevenção e tratamento.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder affecting 2 percent to 5 percent of the population in Western countries. Clinical presentation varies from hyperthyroidism in Graves' Disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. It has been postulated that 79 percent of the susceptibility to develop AITD is attributed to genetic factors, while environmental factors contribute to 21 percent. The identified AITD susceptibility genes include immune-modulating genes, such as the major histocompatibility complex (MHC), cytotoxic T lymphocyte antigen-4 (CTLA-4), CD40 molecule, and protein tyrosine phosphatase-22 (PTPN22), and thyroid-specific genes, including TSH receptor (TSHR) and thyroglobulin (TG). The exact nature of the role environmental factors play in AITD is still not well known, but the involvement of several factors such as iodine diet content, stress, drugs and infections has been reported. However, there is no clear evidence of causality and the mechanisms by which environmental factors trigger thyroid autoimmunity in genetically predisposed individuals remain not fully understood. Knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for prevention and treatment.

Farmacogenética de inibidores seletivos de recaptação de serotonina: uma revisão: [revisão] / Pharmacogenetics of selective serotonine reuptake inhibitors: a review: [revision]

A variabilidade da resposta aos medicamentos se deve em grande parte a fatores genéticos, e essa variabilidade afeta os efeitos terapêuticos e as reações adversas, de forma que a mesma dose de um medicamento pode ser benéfica para um paciente mas ineficaz para outro. Os fármacos conhecidos como inibidores seletivos de recaptação de serotonina (ISRSs) pertencem a uma classe de medicamentos utilizados para o tratamento de uma série de patologias relacionadas com a serotonina, especialmente a depressão. O objetivo deste trabalho é reunir os dados presentes na literatura sobre a associação de genes candidatos com a resposta a ISRSs, fornecendo assim um panorama sobre o estado atual de conhecimento sobre o assunto. A resposta ao tratamento com ISRSs depende da variabilidade de genes codificantes de proteínas envolvidas com o papel da serotonina no cérebro. Com os avanços conquistados a partir do Projeto Genoma Humano, foi possível detectar essas variações, e várias delas mostraram ter importância farmacogenética. Portanto, alguns dos genes relacionados à farmacogenética dos ISRSs já são conhecidos, o que torna clara a necessidade de maiores investigações prospectivas para determinar a real utilidade desse conhecimento na prática clínica, com relação à possibilidade da determinação da dose adequada do fármaco correto para cada paciente, prática que vem sendo denominada de "medicina personalizada".

A large proportion of the variability in drug response is due to genetic factors, and this variability affects therapeutic effects and adverse reactions, so that the same dosage of a drug can be beneficial to some patients, but ineffective to others. The drugs known as selective serotonin reuptake inhibitors (SSRI) belong to a pharmacological class used in the management of a number of diseases related to serotonin, especially depression. The aim of this paper is to collect data from the literature about the association of candidate genes with response to SSRI, providing an overview on the current knowledge of this subject. The effect of SSRI treatment depends on the variability in genes coding proteins involved with the role of serotonin in the brain. The new data from the Human Genome Project allowed detection of these variations, and several of them proved to have pharmacogenetic importance. Therefore, some of the genes related to SSRI pharmacogenetics are already known. This reinforces the need of larger prospective investigations to determine the real use of this knowledge in clinical practice as to the possibility of determining the right dosage, and the right drug to each patient, a practice that has been called "personalized medicine".