Association of serotonin 2A receptor and lack of association of CYP1A2 gene polymorphism with tardive dyskinesia in a Turkish population

The aim of this study was to investigate the possible association of serotonin 2A receptor gene (HTR2A) -1438 G/A polymorphism and CYP1A2 gene 163C/A polymorphism with tardive dyskinesia (TD) in a Turkish population. A total of 47 patients with persistent TD, 80 patients who were consistently without TD, and 100 healthy controls were included in this study. The polymorphic regions of -1438 G/A polymorphism of HTR2A receptor gene (rs6311) and 163C/A of CYP1A2 (rs762551) gene were amplified using polymerase chain reaction (PCR), followed by digestion with restriction enzymes MspI and Bsp1201. Genotype and allele frequencies were calculated by the chi(2)-test. Crude and adjusted odds ratios (ORs) were estimated, and 95% confidence intervals (CIs) were computed by multivariate logistic regression analysis. The genotype and allele frequencies of HTR2A and CYP1A2 gene were similar in schizophrenia with TD, schizophrenia without TD, and healthy controls. The logistic regression analysis showed that cumulative exposure to antipsychotic drugs for every year (p = 0.003; OR = 1.15; CI = 1.07-1.23), and AA genotype of HTR2A gene (p = 0.0258; OR = 4.34; CI = 1.19-15.81) are risk factors for TD. The same logistic regression model showed no association between CYP1A2 polymorphism and TD. The results of the present study seem to indicate that HTR2A gene polymorphism influences the tendency to express TD following prolonged antipsychotic drug exposure in Turkish schizophrenia patients.     

The association between catechol-O-methyl-transferase Val108/158Met polymorphism and suicide

One of the candidate genes for suicide is also a gene in the pathway for catecholamine degradation encoding an enzyme catechol-O-methyl-transferase (COMT). It harbors a common functional polymorphism, a G to A nucleotide transition resulting in amino acid substitution from valine (Val) to methionine (Met) at position 158 (COMT Val(108/158) Met; rs4680), that has been associated with psychiatric disorders characterized with an increased risk of suicidal behavior. We have performed the first study on Caucasian population examining the association between completed suicide and the COMT Val(108/158) Met polymorphism. The study population consisted of 356 suicide victims and 198 control subjects. Significant difference in COMT Val(108/158) Met variants' (genotypes, alleles and Val carriers) distribution was found only in male groups, between controls and suicide victims (P = 0.018, P = 0.031, P = 0.005), and between controls and violent suicide victims (P = 0.026, P = 0.042, P = 0.010). The r value from the standardized residuals showed that the Met/Met genotype (r = 2.03) in the control group contributed to these significant differences. In contrast to male subjects, no significant differences in the frequency of the COMT Val(108/158) Met variants were detected between female control and female suicide groups; however, the power of calculation (range 0.161-0.680) was below the desired 0.800. In addition, the logistic regression analysis confirmed these significant differences. In conclusion, our results showed the overpresentation of the Met/Met genotype in male control subjects compared with male suicide victims, suggesting that this genotype of the COMT Val(108/158) Met might be a protective factor against suicide.     

Regional Distribution and Relative Abundance of Serotonin2c Receptors in Human Brain: Effect of Suicide

Abnormalities in serotonin receptor subtypes have been observed in the postmortem brain of suicide victims. We examined the regional distribution of serotonin (5HT)(2C) receptor mRNA in several areas of the human brain and also compared its protein and mRNA expression in the prefrontal cortex (PFC), hippocampus, and choroid plexus between suicide victims and normal control subjects. 5HT(2C) receptors were found to be distributed in several areas of the human brain (in order of abundance): highly concentrated and richest in choroid plexus; hypothalamus; nucleus accumbens; with the lowest abundance in PFC and cerebellum. Comparison of 5HT(2C) receptors between suicide victims and control subjects showed higher protein levels in the PFC but not the hippocampus or choroid plexus of suicide victims. However, there were no significant differences in mRNA levels between suicide victims and control subjects in these brain areas. These results suggest that 5HT(2C) receptors are richly distributed throughout the brain with the highest level in the choroid plexus and that abnormalities in protein expression of 5HT(2C) receptors in the PFC may be associated with suicide.     

Screening the human serum proteome for genotype-phenotype associations: an analysis of the IL6 -174G>C polymorphism

Interleukin (IL)-6 is a circulatory, pleiotropic cytokine with multiple roles in the immune system. Both IL-6 and the IL6 -174G>C promoter polymorphism have been linked to various diseases associated with inflammation. However, the mechanism by which the polymorphism influences disease risk is unclear. We postulated that serum proteome analysis of individuals with different IL6 -174G>C genotypes would provide insight on genotype-phenotype associations of this polymorphism and its role in disease susceptibility. Serum from a random sample of control participants in an ongoing population-based case-control study of non-Hodgkin lymphoma was pooled by IL6 genotype and used to screen for the optimal SELDI-TOF MS arrays for analysis. We report differences in serum protein expression of individuals with specific genotypes based on pooled and individual sample analysis. In particular, we report an association of the -174C allele with increased apolipoprotein C-I (ApoC-I). Additionally, we corroborate previous findings of an association of the -174C allele with lower autoantibodies to heat shock protein 60 and confirm the absence of any association between the IL6 -174G>C genotype and serum IL-6 levels. This study illustrates that proteome analysis can enhance our understanding of genotype-phenotype relationships. Additional studies are needed to clarify the interaction between the IL6 -174G>C polymorphism and ApoC-I.     

Vascular gene polymorphisms (EDNRA -231 G>A and APOE HhaI) and risk for migraine

Migraine is a neurovascular disorder, and hence, any alteration in vascular endothelial function by either the endothelin system or the apolipoproteins may contribute to its pathophysiology. Thus, we investigated the role of EDNRA -231 G>A and APOE HhaI polymorphism for a possible association with migraine. Genotyping of 613 subjects consisting of 217 migraine subjects, 217 healthy controls (HC), and 179 subjects with tension-type headache was performed using the standard PCR-RFLP method. Data were analyzed by taking the Bonferroni-corrected p-values into account. We found significant difference in the frequency of EDNRA AA genotype between migraine subjects when compared with HC (p-value?=?0.005; OR?=?2.542; confidence interval [CI]?=?1.329-4.863). A similar trend was shown by female migraine subjects at genotype and allele levels. The association of EDNRA -231 G>A polymorphism with migraine fit a recessive model (migraine vs. HC, p-value?=?0.002; OR?=?1.917; CI?=?2.268-2.898). Female migraineurs without aura (MO) followed a similar trend. In the case of APOE HhaI polymorphism, E3E4 and E2E3 genotypes conferred risk when taken together in case of migraine versus HC (p-value?=?0.005; OR?=?2.715; CI?=?1.342-5.490) and migraine with aura (MA) versus HC (p-value?=?0.004; OR?=?3.422; CI?=?7.992). The risk was also seen after stratification on the basis of gender in female migraineurs (total migraine and MA). The interaction of EDNRA and APOE genotypes did not show further significance. The AA genotype and A allele of EDNRA -231 G>A polymorphism conferred risk for total migraine and MO. In APOE HhaI polymorphism, E3E4 and E2E3 conferred risk when taken together in total migraine and MA.     

Six novel single-nucleotide polymorphisms in SPAG11 gene and their association with sperm quality traits in Chinese Holstein bulls

Sperm-associated antigen 11 (SPAG11) is predominant in the male reproductive tract. Similar to β-defensin, aside from its antibacterial activity, SPAG11 also has an important role in male reproductive function. In the present study, the association of bovine SPAG11 gene polymorphism with sperm quality traits was examined, including ejaculate volume, sperm concentration, fresh sperm motility, post-thaw cryopreserved sperm motility, and deformity rate of bull semen. Six novel single nucleotide polymorphisms (SNPs) of the SPGA11 gene were investigated in 426 normal mature Chinese Holstein bulls using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), PCR-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR), and DNA sequencing methods. Linkage disequilibrium analysis showed that g.1306G>A and g.1454G>A (SNP-1), and g.16904G>T, g.16974C>T, and g.17000A>G (SNP-2) are completely linked, respectively. Correlation analysis showed the SNP-2 marker had a marked effect on fresh sperm motility and sperm concentration (P<0.05). SNP-3 g.22696T>C had a marked effect on post-thaw cryopreserved sperm motility (P<0.05) and deformity rate (P<0.01). However, the presence of SNP-1 was not correlated with the sperm production traits (P>0.05). Furthermore, association analyses of the 8 haplotypes constructed from the 17 combined haplotypes and reproductive traits showed that the bulls with the combined haplotype H5H6 (GGT/TTC) have the highest ejaculate volumes and the bulls with combined haplotypes H1H1 (AAT/TTT) and H1H6 (AGT/TTC) had the highest fresh and post-thaw sperm motilities, respectively. These results indicate that new molecular markers associated with sperm quality traits can be used in marker-assisted selection in bull breeding programs.     

Does genetic background moderate the association between parental education and school achievement?

This study was conducted with a purpose to examine whether the T102C polymorphism of the serotonin receptor 2A (HTR2A) gene moderates the association between parental education and children's school achievement across nine compulsory school years. The study was carried out in a population‐based sample of Finnish students (aged 9, 12 and 15 years, n = 982). It was found that the HTR2A gene was not related to the school achievement at any school level, but moderated the association between maternal education and the children's grade point averages. The T/T genotype carriers benefited most from high‐maternal education, and suffered from a low one more than the carriers of the other variants of the HTR2A gene. The present finding may at least partly answer the important question why academic outcomes of environmental interventions vary even at the same intelligence levels of the students.     

PTGS2 (COX2)??765G>C gene polymorphism and risk of sporadic colorectal cancer in Iranian population

Colorectal cancer (CRC) is one of the leading cancers worldwide. Through genome wide association studies, several single nucleotide polymorphisms scattered in the genome emerged to be influential in the development of sporadic CRC in some populations. However, replicative studies failed to prove a particular SNP-CRC association in populations and ethnic groups. Cyclooxygenase-2 (PTGS2) is a crucial enzyme involved in the metabolism of prostaglandins. The aim of this replicative study is to investigate the possible association between PTGS2?-765G>C polymorphism and sporadic CRC risk in a subset of Iranian population. A total of 110 patients with sporadic CRC, and 120 controls were genotyped for PTGS2?-765G>C polymorphism by using polymerase chain reaction-based restriction fragment length polymorphism. There were no significant differences in the genotype and allele frequencies of PTGS2?-765G>C between two groups except in irregular aspirin or non-steroidal anti-inflammatory drugs (NSAID) consumers. Frequencies of genotypes and alleles were as follows: GG?=?44.2, GC?=?48.3, CC?=?7.5%, in controls and GG?=?34.55, GC?=?60.9, CC?=?4.55% in cases. Regarding the allele frequency, the following values were found: G?=?65, C?=?35% in cases and 68.3, 31.7% in the controls, respectively. In irregular aspirin or NSAID consumers combined GC+CC genotype was found to be a risk genotype (OR?=?1.933, 95% CI: 1.067-3.501, P?=?0.036). Overall, no significant relation was found between this polymorphism and sporadic CRC in Iranians. However, in irregular aspirin or NSAID consumers the combined GC+CC genotype proved to be a risk genotype.     

The association between the T102C polymorphism of the HTR2A serotonin receptor gene and HDL cholesterol level in Koreans

5-HT2A is one of major serotonin receptor that is involved in the action of serotonin-targeting drugs. Previous clinical studies have shown an unexpected association between lower cholesterol level and psychiatric diseases, in which T102C polymorphism of HTR2A, gene of 5-HT2A serotonin receptor, might be involved. Therefore, we hypothesized a potential association between lower cholesterol level and T102C polymorphism. The effect of the T102C polymorphism on the serum lipid profiles of 646 subjects without specific psychiatric disease was investigated. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. There were significantly lower levels of total cholesterol (193.6 +/- 35.0 versus 202.1 +/- 45.5 mg/dl, p = 0.016) and HDL-cholesterol (42.7 +/- 11.6 versus 46.3 +/- 12.7 mg/dl, p = 0.004) in CC genotype than non-CC genotypes. Moreover, multivariate analysis showed that the CC genotype is a strong predictor of a lower HDL-cholesterol level (p < 0.001). In conclusion, this study shows that the CC genotype of the HTR2A gene is related to lower HDL-cholesterol level in Koreans. This is the first demonstration showing the potential genetic relationship between the serotonin receptor gene polymorphism and the HDL-cholesterol level.     

Vascular endothelial growth factor gene polymorphisms and colorectal cancer risk: a meta-analysis

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth and metastasis. Polymorphisms of the VEGF gene have been associated with susceptibility to colorectal cancer (CRC). However, the specific association still remains controversial. We made a meta-analysis of the association between VEGF gene polymorphisms and CRC risk. Only eight case-control studies were retrieved, with a total of 2337 CRC patients and 2032 healthy controls. Six VEGF gene polymorphisms were addressed in all studies included, +936C>T (rs3025039), -2578C>A (rs699947), -1154G>A (rs1570360), -634G>C (rs2010963), -460C>T (rs833061), and +405C>G (rs2010963). There was a significant association between -2578C>A polymorphism and susceptibility to CRC in the comparison of C allele carriers (CC + CA) versus AA (odds ratio = 0.77, 95% confidence interval = 0.62-0.96, P = 0.02). No association was found between +936C>T, -1154G>A, -634G>C, -460C>T, and +405C>G with susceptibility to CRC. We conclude that the C allele carrier (CC + CA) of VEGF -2578C>A polymorphism appears to be a protective factor for CRC.     

Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes

Several studies suggest involvement of serotoninergic system in the pathophysiology of Autism Spectrum Disorder (ASD). The 5-HT receptor binding studies using ³H-lysergic acid diethylamide (³H-LSD) and linkage analysis provided evidences to consider HTR2A as a potential candidate gene for ASD. The three SNPs, −1438A/G (rs6311), 102T/C (rs6313) and 1354C/T (rs6314) of HTR2A have been well studied in the etiology of various neuropsychiatric disorders. But studies on association of this gene with ASD are limited to two reports from American and Korean populations. Additionally there are reports, which demonstrated paternal imprinting of HTR2A with expression from only one allele. So far no reports are available on HTR2A and its association with any neuropsychiatric disorders from Indian population. Therefore, the present study investigates association of the above mentioned three markers of HTR2A with ASD in Indian population using population and family-based approaches. The study also deals with allelic expression pattern of HTR2A in Peripheral Blood Leukocytes (PBLs) to understand the parental imprinting status. The genotyping analyses were carried out for probands, parents and controls. The subsequent association analyses did not show association of these markers with ASD. So, HTR2A is unlikely to be a genetic marker for ASD in Indian population. The expression analyses showed absence of monoallelic expression, suggesting lack of parental imprinting of HTR2A gene. However, we noticed methylation of the CpG sites at −1438A/G and 102T/C loci of HTR2A gene. Further bioinformatics analysis revealed absence of CpG islands in the promoter of the gene supporting biallelic expression pattern of HTR2A in PBLs.     

Investigation on BRCA1 SNPs and its effects on mastitis in Chinese commercial cattle

The main objective of this study was to investigate whether the bovine breast cancer 1 (BRCA1) gene was associated with mastitis resistance in Chinese commercial cattle. A total of 51 SNPs were screened from public data resources and DNA sequencing. Three SNPs (c.5682G>C,c.26198C>T and c.46126G>T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and created restriction site PCR (CRS-PCR) methods and 21 combinations of these SNPs were observed. The single SNP and their genetic effects on somatic cell score (SCS) were evaluated and a significant association with SCS was found in c.46126G>T. The mean SCS of individuals with genotype KK was significantly lower than those of genotypes KL and LL. The results of combined genotypes analysis of three SNPs showed that HHLLNN genotype with the highest SCS was easily for the mastitis susceptibility, whereas GGKKMM genotype with the lowest SCS was favorable for the mastitis resistance. The information provided in the present study will be very useful for improving mastitis resistance in dairy cattle by marker-assisted selection (MAS).     

Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes

Several studies suggest involvement of serotoninergic system in the pathophysiology of Autism Spectrum Disorder (ASD). The 5-HT receptor binding studies using ³H-lysergic acid diethylamide (³H-LSD) and linkage analysis provided evidences to consider HTR2A as a potential candidate gene for ASD. The three SNPs, −1438A/G (rs6311), 102T/C (rs6313) and 1354C/T (rs6314) of HTR2A have been well studied in the etiology of various neuropsychiatric disorders. But studies on association of this gene with ASD are limited to two reports from American and Korean populations. Additionally there are reports, which demonstrated paternal imprinting of HTR2A with expression from only one allele. So far no reports are available on HTR2A and its association with any neuropsychiatric disorders from Indian population. Therefore, the present study investigates association of the above mentioned three markers of HTR2A with ASD in Indian population using population and family-based approaches. The study also deals with allelic expression pattern of HTR2A in Peripheral Blood Leukocytes (PBLs) to understand the parental imprinting status. The genotyping analyses were carried out for probands, parents and controls. The subsequent association analyses did not show association of these markers with ASD. So, HTR2A is unlikely to be a genetic marker for ASD in Indian population. The expression analyses showed absence of monoallelic expression, suggesting lack of parental imprinting of HTR2A gene. However, we noticed methylation of the CpG sites at −1438A/G and 102T/C loci of HTR2A gene. Further bioinformatics analysis revealed absence of CpG islands in the promoter of the gene supporting biallelic expression pattern of HTR2A in PBLs.     

Role of NQO1 609C>T and NQO2-3423G>A polymorphisms in susceptibility to gastric cancer in Kashmir valley

NADPH: quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside: quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze reductive activation of carcinogens from cigarette smoke, such as nitrosamines and heterocyclic amines. These enzymes also protect cells against oxidative damage from reactive oxygen species. The present study investigated the associations of genetic variants of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to gastric cancer (GC) as well as their interactions with known risk factors in Kashmir valley. A case control study was performed in 303 subjects (108 GC and 195 healthy controls). All subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed by chi-square test and logistic regression model. The NQO1 609C>T TT genotype and T allele were significantly associated with increased risk for GC, whereas NQO2 -3423G>A polymorphism did not show any association with GC. Also, NQO1 609C>T TT genotype showed significant association with gastric adenocarcinoma. The interaction of NQO1/NQO2 genotypes with high consumption of salted tea, a known risk factor, did not further modulate the risk of GC. In conclusion, NQO1 609C>T polymorphism shows association with GC risk in Kashmir valley.     

Lack of an association between -308G>A polymorphism of the TNF-α gene and liver cirrhosis risk based on a meta-analysis

TNF-α is a potential proinflammatory cytokine that plays an important role in the pathogenesis of liver cirrhosis. We investigated a possible association between TNF-α -308G>A polymorphism and liver cirrhosis risk by conducting a meta-analysis. Publications addressing the association between TNF-α -308G>A and liver cirrhosis risk were selected from the Pubmed and Embase databases. Data were extracted from the studies by two independent reviewers; odds ratio (OR) with a 95% confidence interval (CI) was calculated from these data. The meta-analysis was performed by Review Manager Version 5.0.24 and STATA Version 9.2. Eleven studies were retrieved, reporting a total of 1796 liver cirrhosis cases and 2113 healthy controls. A meta-analysis of these 11 studies identified no significant association between TNF-α -308G>A polymorphism and liver cirrhosis risk in all comparisons of G vs A allele; GG vs GA + AA; GG + GA vs AA; GG vs AA; GG vs GA (OR = 1.14, 95%CI = 0.85-1.55, P = 0.38; OR = 1.24, 95%CI = 0.87- 1.77, P = 0.24; OR = 0.90, 95%CI = 0.62-1.30, P = 0.57; OR = 1.03, 95%CI = 0.56-1.89, P = 0.92; OR = 1.30, 95%CI = 0.90-1.88, P = 0.17; respectively). In conclusion, we found no association between TNF-α -308G>A polymorphism and liver cirrhosis risk, both in Caucasian and Asian populations.     

Incidence and Risk Factors of Homicide–Suicide in Swiss Households: National Cohort Study

Background

Homicide–suicides are rare but catastrophic events. This study examined the epidemiology of homicide-suicide in Switzerland.

Methods

The study identified homicide–suicide events 1991–2008 in persons from the same household in the Swiss National Cohort, which links census and mortality records. The analysis examined the association of the risk of dying in a homicide–suicide event with socio-demographic variables, measured at the individual-level, household composition variables and area-level variables. Proportional hazards regression models were calculated for male perpetrators and female victims. Results are presented as age-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI).

Results

The study identified 158 deaths from homicide–suicide events, including 85 murder victims (62 women, 4 men, 19 children and adolescents) and 68 male and 5 female perpetrators. The incidence was 3 events per million households and year. Firearms were the most prominent method for both homicides and suicides. The risk of perpetrating homicide-suicide was higher in divorced than in married men (HR 3.64; 95%CI 1.56–8.49), in foreigners without permanent residency compared to Swiss citizens (HR 3.95; 1.52–10.2), higher in men without religious affiliations than in Catholics (HR 2.23; 1.14–4.36) and higher in crowded households (HR 4.85; 1.72–13.6 comparing ≥2 with <1 persons/room). There was no association with education, occupation or nationality, the number of children, the language region or degree of urbanicity. Associations were similar for female victims.

Conclusions

This national longitudinal study shows that living conditions associated with psychological stress and lower levels of social support are associated with homicide-suicide events in Switzerland.     

Fatty acid composition of the postmortem prefrontal cortex of adolescent male and female suicide victims

Prior epidemiological, prospective intervention, and peripheral and central fatty acid composition studies suggest that omega-3 fatty acid deficiency may be associated with the pathoaetiology of depression and suicide. In the present study, we determined the fatty acid composition of the postmortem prefrontal cortex (PFC) of adolescent male and female suicide victims and age-matched controls. Fatty acid composition (wt% total fatty acids) and concentrations (μmol/g) were determined in the postmortem PFC (Brodmann area 10) of male and female adolescent (aged 13–20 years) suicide victims (n=20) and age-matched controls (n=20) by gas chromatography. None of the major polyunsaturated fatty acids including the principle brain omega-3 fatty acid, docosahexaenoic acid (DHA), monounsaturated fatty acids, or saturated fatty acids differed significantly between adolescent suicide victims and controls before or after segregation by gender. The arachidonic acid (AA, 20:4n-6): DHA ratio and adrenic acid (22:4n-6) composition were negatively correlated with age at death in controls but not in suicides, and males exhibited a greater AA:DHA ratio irrespective of cause-of-death. These results demonstrate that adolescent male and female suicide victims do not exhibit DHA deficits in the postmortem PFC relative to age-matched controls, and suggest that suicide victims do not exhibit the normal age-related decrease in adrenic acid composition and the AA:DHA ratio.     

The interaction between TPH2 promoter haplotypes and clinical-demographic risk factors in suicide victims with major psychoses

Tryptophan hydroxylase isoform 2 (TPH2) is a rate-limiting enzyme in the biosynthesis of serotonin (5-HT) and is predominantly localized in the brain. Previous studies have suggested that there is an association between serotonergic dysfunction in the brain and suicidality. This study was designed to examine whether the -473T > A and -8396G > C polymorphisms of the TPH2 gene may be associated with completed suicide in subjects with major psychoses from the Stanley Foundation Brain Bank sample. TPH2 genotypes were determined in 69 subjects with a diagnosis of schizophrenia or bipolar disorder, among which 22 died by suicide. Genomic DNA was amplified by polymerase chain reaction and typed by automated methods. Both markers were found to be in Hardy-Weinberg equilibrium and in strong linkage disequilibrium. No association with history of suicide was found for either polymorphism. Haplotype analysis with EHAP showed no association between completed suicide and haplotype distribution (chi2 = 1.877; 3 df; P = 0.598). Nor was there any association between suicide and these genetic markers even when clinical-demographic factors were considered as covariates in the haplotype analysis. These findings suggest that these 5' marker haplotypes in the TPH2 gene do not influence suicidal behaviour.     

The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin

The bile acid-activated nuclear receptor farnesoid X receptor (FXR) plays an important role in lipid and glucose metabolism, and in addition, it regulates multiple drug transporters involved in statin disposition. We examined whether a functional single nucleotide polymorphism (SNP) in FXR (-1G>T) influenced the lipid-lowering effect of rosuvastatin. In 385 Chinese patients with hyperlipidemia who had been treated with rosuvastatin 10 mg daily for at least 4 weeks, the association between the FXR -1G>T SNP and lipid response to rosuvastatin was analyzed. The FXR -1G>T SNP was not associated with baseline lipids but was significantly associated with the LDL cholesterol (LDL-C) and total cholesterol response to rosuvastatin. Carriers of the T-variant allele (GT+TT = 68+3) had 4.4% (95% CI: 1.2, 7.5%, P = 0.006) and 2.6% (95% CI: 0.3, 5.0%; P < 0.05) greater reductions in LDL-C and total cholesterol, respectively, compared with those with homozygous wild-type alleles. The association between the FXR polymorphism and the LDL-C response to rosuvastatin remained significant after adjusting for other covariants. This association of the variant allele of the FXR -1G>T polymorphism with a greater LDL-C response to rosuvastatin may suggest that this polymorphism influences the expression of the hepatic efflux transporters involved in biliary excretion of rosuvastatin.