GG Genotype Group Research Articles

Low-Density Lipoprotein Receptor Apolipoprotein B Gene Polymorphism in Kurdish Patients With Severe Hypercholesterolemia.

Background Polymorphisms in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB-100) genes have been linked to severe hypercholesterolemia in several populations. This study investigated the frequency of LDLR-Ava II and APOB-Xba I polymorphisms among Kurdish patients with severe hypercholesterolemia. Methodology We investigated LDLR-Ava II and APOB-Xba I gene polymorphisms in Kurdish patients attending the Duhok Specialized Laboratory Center in Duhok, Kurdistan Region, Iraq. We included a total of 80 subjects in this study, of which 40 (20 males and 20 females) had severe hypercholesterolemia, and 40 apparently healthy volunteers (21 males and 19 females) had normocholesterolemia, served as a control group. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to determine the polymorphisms of the LDLR-Ava II and APOB-Xba I genes. Results In those with severe hypercholesterolemia, the observed allele frequencies were AA LDLR-Ava II polymorphism (eight, 20%) followed by TT APOB-Xba I polymorphisms (six, 15%), whereas these frequencies were five (12.5%) and one (2.5%) in those with normocholesterolemia, respectively. The AA genotype group had considerably higher cholesterol and LDL-C levels compared with the GG genotype group. A similar pattern was observed when comparing the TT and CC genotype groups. Conclusions Our results showed a high frequency of AA LDLR-Ava II polymorphism in conjunction with TT APOB-Xba I polymorphism which may be strongly associated with hypercholesterolemia in the Kurdish population.

A Comparative Study of ALDH2 rs671 Gene and Physical Characteristics and Fitness of Sports Prodigies

PURPOSE: This study aimed to identify differences in physique, basic physical fitness, and specific physical fitness based on the classification of the ALDH2 gene in sports prodigies.METHODS: This study tested the ALDH2 gene in 30 sports prodigies (18 males and 12 females). The participants’ physique (height, weight, arm and leg length, arm stretch, and thigh circumference), body composition (lean body mass and body fat), basic physical fitness (grip strength, sit-ups, sit-and-reach, T-wall test, light reaction time, and standing long jump), and specific physical fitness (shuttle run, sit and throw, sprint, and graded exercise test) were measured.RESULTS: There were no significant differences between the groups classified by gene type in terms of physique, body composition, or specific physical fitness (p>.05). However, in terms of basic physical fitness, only sit-ups showed a significant difference based on the gene classification (p<.05).CONCLUSIONS: The GG genotype group demonstrated superior physical fitness compared to the A allele group when tested for ALDH2. Therefore, ALDH2 gene testing is necessary for classifying physical fitness and designing personalized training programs.

Impact of MAOA Gene Polymorphism on the Efficacy of Antidepressant Treatment and Craving Severity for Betel Quid Use Disorder.

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 (p = 0.0194), 4 (p = 0.0078), 6 (p = 0.0277), and 8 (p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 (p = 0.0313), 4 (p = 0.0134), 6 (p = 0.0061), and 8 (p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score (p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.

Association between uncoupling protein 1-3826 A/G polymorphism and the effects of anaerobic exercises on serum oxidative stress

ObjectivesAerobic exercise promotes uncoupling protein-1 (UCP-1) induced white adipose tissue browning by increasing serum nitric oxide (NO), irisin and interleukin-6 (IL-6). However, oxidative stress (OS) occurring during anaerobic exercise downregulates UCP-1. Moreover, UCP-1-3826 A/G polymorphism (UCP1P) is associated with weight gain due to impaired thermogenesis which may be due to UCP1P induced modification in OS. Therefore, our purpose was to investigate the role of UCP1P on the effects of acute maximal exercise (AME) and chronic anaerobic exercise (CAT) on serum OS, UCP-1, NO, irisin and IL-6 levels. Equipments and methodsSport group (SG, n=43) was formed of anaerobic athletes, while control group (CG, n=43) comprised physically inactive men. Postprandial blood was taken from SG and CG before and after AME to determine serum UCP-1, irisin, IL-6, NO, and oxidative stress index (OSI=total oxidant/antioxidant status [TOS/TAS] ratio). To investigate the effects of CAT on serum parameters, SG and CG's results were compared. UCP1P was determined by restriction fragment length polymorphism analysis. ResultsAME significantly increased all parameters in SG and CG (P<0.05). However, CAT increased only OSI and IL-6 (P<0.05), decreased UCP-1 and TAS and did not affect TOS, NO and irisin. OSI of GG homozygous athletes were significantly higher than other genotype groups (P<0.05). Although significant negative correlations were found between UCP-1 and OS markers in GG and AA genotype groups before AME, significant positive correlations were found between UCP-1 and TAS in AA genotype group after AME. GG homozygous athletes may be more prone to higher OS. Decrease in UCP-1 due to CAT may be affected by GG genotype group's genetic disposition for OS.

SLC2A9 rs1014290 Polymorphism is Associated with Prediabetes and Type 2 Diabetes.

To investigate the association of the A/G rs1014290 polymorphism in SLC2A9 with type 2 diabetes (T2DM) and prediabetes mellitus (pre-DM). Patients and Methods. We enrolled 1058 patients who attended the Hebei General Hospital, Shijiazhuang, Hebei Province, China. The patients underwent general testing and oral glucose tolerance tests and were divided into three groups: 352 patients newly diagnosed with T2DM, 358 patients with pre-DM, and 348 healthy controls. The single nucleotide polymorphism (SNP) was detected by ligase detection reactions. The χ 2 test, one-way ANOVA, and binary logistic regression analysis were used to analyze the results. In the T2DM group, the GG genotype frequency at the rs1014290 locus was significantly lower (14.8%) than it was in the healthy controls. Furthermore, the GG genotype group was associated with a reduced risk of T2DM in unadjusted and confounder-adjusted models compared with the risk in the AA genotype group. The G allele in the SLC2A9 rs1014290 locus decreased susceptibility to T2DM. In the pre-DM group, the GG and AG genotype groups had no significant correlation with the risk of pre-DM in any of the models. In the T2DM group, the uric acid level was significantly lower in the GG genotype group. In the T2DM and pre-DM groups, the HOMA-β levels were significantly higher in the GA (P < 0.001) and GG (P < 0.001) genotype groups than it was in the AA genotype group, and HOMA-IR was significantly lower in the GA (P < 0.001) and GG (P < 0.001) genotype groups than it was in the AA genotype group. The A/G (rs1014290) SNP in SLC2A9 is closely related to the occurrence and development of diabetes.

NLRP3 Susceptible Gene Polymorphisms in Patients with Primary Gouty Arthritis and Hyperuricemia.

Polymorphisms have been identified to predispose to primary gouty arthritis (GA) and hyperuricemia (HUA). Here, we accessed the five polymorphisms of rs10754558, rs35829419, rs3738448, rs3806268, and rs7525979 in NLRP3 on GA and HUA susceptibility. We collected 1198 samples (314 GA, 377 HUA, and 507 controls) for this case-control study. Our data detected that the rs3806268 (GA vs. AA: OR = 0.65, p = 0.012) was significantly associated with the susceptibility to GA. The rs3738448 (TT vs. GG: OR = 2.05, p = 0.024) and rs7525979 (TT vs. CC: OR = 1.96, p = 0.037) were significantly associated with the susceptibility to HUA. The rs3806268 AG genotype presented decreased risk of GA among the hypertension (OR = 0.54, p = 0.0093), smoking (OR = 0.59, p = 0.018), and no obesity (OR = 0.60, p = 0.0097) subjects compared to the GG genotype group. The rs3738448 TT genotype demonstrated increased risk of HUA among the hypertension (OR = 4.10, p = 0.0056) and no drinking population (OR = 3.56, p = 0.016) compared to the GG genotype group. The rs7525979 TT genotype demonstrated increased risk of HUA among the hypertension (OR = 4.01, p = 0.0064) and no drinking population (OR = 3.24, p = 0.034) compared to the CC genotype group. Furthermore, a significant haplotype effect of rs10754558/C-rs35829419/C-rs3738448/G-rs3806268/A-rs7525979/C was found (OR = 1.60, p = 0.0046) compared with GCGAC haplotype. Bioinformatics analyses indicated that rs3738448, rs3806268, and rs7525979 might influence the gene regulation, while the T-allele of rs3738448 increased the stability of NLRP3-mRNA. Collectively, our case-control study confirms NLRP3 polymorphisms might participate in regulating immune and inflammation responses in GA and HUA.

AMER3 variants modify the U-shaped association of urinary total hydroxyphenanthrene with fasting plasma glucose: A newfound gene-environment interaction

As a polycyclic aromatic hydrocarbon, environmental exposure to phenanthrene is widespread worldwide. The potential effects and mechanism of phenanthrene exposure on fasting plasma glucose (FPG) have not been well determined. In this study, we aim to explore the effects of phenanthrene exposure and AMER3 variants on fasting plasma glucose (FPG) through a longitudinal epidemiological study. Repeated measurements of five urinary hydroxyphenanthrene (OHPh) for 5739 participants with 7083 observations from the Wuhan-Zhuhai cohort were performed to analyze the relationships between total OHPh (ΣOHPh) and FPG using linear mixed models and restricted cubic spline functions. Then, we genotyped 2777 participants (4104 observations) using the Infinium OmniZhongHua-8 BeadChip and included all 14 single nucleotide polymorphisms (SNPs) within the AMER3 gene to analyze the interaction of the AMER3 on the relationship between ΣOHPh and FPG. We observed a U-shaped relationship between ΣOHPh and FPG, and the turning point of ΣOHPh was 2.512 μg/mmol Cr. When lower than the turning point, ΣOHPh was negatively associated with FPG, while higher than the turning point, ΣOHPh was positively associated with FPG. Furthermore, we observed interactions (Pint <0.05) between two common variants (rs72854995 and rs72854999) of the AMER3 and ΣOHPh on FPG change: the U-shaped relationship was still observed in the GG genotype groups but not in the allele A carriers. Our results suggested that the AMER3 gene can modify the U-shaped relationship between phenanthrenes exposure and FPG, which showed a new gene-environment interaction and will provide a new perspective on the relationship between phenanthrene exposure and FPG.

Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4mg BUP (BUP4), 16mg BUP (BUP16), or placebo (PLB) for 8weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

A NOS1AP gene variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin.

Digoxin is characterized by a small therapeutic window and a QT-interval shortening effect. Moreover, it has been shown that the genetic variants of the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. We investigated whether the rs10494366 variant of the NOS1AP gene decreases the QT-interval shortening effect of digoxin in patients using this drug. We included 10,057 individuals from the prospective population-based cohort of the Rotterdam Study during a median of 12.2 (interquartile range (IQR) 6.7-18.1) years of follow-up. At study entry, the mean age was 64 years and almost 59% of participants were women. A total of 23,179 ECGs were longitudinally recorded, of which 334 ECGs were from 249 individuals on digoxin therapy. The linear mixed model analysis was used to estimate the effect of the rs10494366 variant on the association between digoxin use and QT-interval duration, adjusted for age, sex, RR interval, diabetes, heart failure, and history of myocardial infarction. In non-users of digoxin, the GG genotype was associated with a significant 6.5 ms [95% confidence interval (CI) 5.5; 7.5] longer QT-interval duration than the TT variant. In current digoxin users, however, the GG variant was associated with a significantly -23.9 [95%CI -29.5; -18.5] ms shorter mean QT-interval duration than in those with the TT variant with -15.9 [95%CI -18.7; -13.1]. This reduction was strongest in the high digoxin dose category [≥0.250 mg/day] with the GG genotype group, with -40.8 [95%CI -52.5; -29.2] ms changes compared to non-users. Our study suggests that the minor homozygous GGgenotype group of the NOS1AP gene rs10494366 variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin in a population of European ancestry.

Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder.

BackgroundOxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD.Methods SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD = 75; healthy controls = 72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (prefrontal cortex [PFC], caudal anterior cingulate cortex, hippocampus) and for vertex-wise whole-brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume, area, and thickness analyses.ResultRegions of interest analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for caudal anterior cingulate cortex volume and surface area as well as PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs the healthy controls GG genotype group. There was a significant BD diagnosis × GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group.ConclusionWe found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structures in youth with BD in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.

The Polymorphism in Interleukin-6-597 G/A Gene and their Levels on Type 2 Diabetic Patients

BACKGROUND: Interleukin-6 (IL-6) pro-inflammatory cytokines play a role in the pathogenesis of inflammatory reactions in type 2 diabetes mellitus (T2DM). The -597G/A is one of IL-6 gene polymorphisms that are associated with the T2DM risk.&#x0D; AIM: This study aimed to observe the polymorphism in IL-6-597 G/A gene and their levels on type 2 diabetic patients at Universitas Sumatera Utara Hospital.&#x0D; MATERIALS AND METHODS: IL-6 -597 G/A gene polymorphisms and levels were done in 80 type 2 diabetic patients. The levels of IL-6 were performed by enzyme-linked immunosorbent assay method. Analysis of IL-6-597 G/A gene polymorphism was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism. The PCR products were cut by FokI restriction enzyme and then visualized with 4% agarose.&#x0D; RESULTS: This study showed that the genotype frequency of GG and GA was 97.5 % and 2.5 %, respectively; however, no A/A genotype shown in this population. IL-6 levels were higher in GG genotype group compare to GA+AA genotype group, with the association were significant (p &lt; 0.05).&#x0D; CONCLUSION: This study indicated that GG genotype was common genotype in the IL-6-597 G/A gene polymorphism and the polymorphism was significantly with the IL-6 levels.

Effects of the DMRT1 genotype on the body weight and gut microbiota in the broiler chicken

Intestinal microbiota is a critical determinant of growth and risk of metabolic diseases. Our previous studies showed that the locus rs16775833 within the DMRT1 gene is significantly associated with variation in the population structure of the gut microbiota, which is involved in determining the BW of the chicken. To assess the accuracy of correlation of rs16775833 located in the DMRT1 gene on microbial population and BW in birds, 2 genotypes GG and TT in the rs16775833 were identified in Chinese Yellow broiler breeders. We found that BW in the TT genotype group was significantly higher than in the GG genotype group at 7 and 13 wk of age in 777 female chickens. A full-length 16S rRNA sequencing approach was used to further evaluate the fecal bacterial composition of female broilers in 11 TT genotype chickens with high weight (HW-TT) and 11 GG genotype chickens with low weight (LW-GG) at 91 D of age. Partial least squares discriminant analysis revealed that the microbiota of the HW-TT and LW-GG females were clearly separated into 2 clusters. Furthermore, we identified 13 significantly different (P < 0.05) microbes at the genus level and 17 significantly different (P < 0.05) species between the HW-TT and LW-GG groups. Our data show that rs16775833 can modulate the microbial community structure and is associated with the BW of birds. To our knowledge, this is the first time that DMRT1 has been identified as a specific host factor, which is not only involved in sex determination but also has an effect on microbial function that might regulate animal growth.

Relations between early maternal sensitivity and toddler self-regulation: Exploring variation by oxytocin and dopamine D2 receptor genes.

Gene-by-environment interactions between maternal sensitivity during infancy and child oxytocin receptor gene (OXTR rs53576) and D2 dopamine receptor gene (DRD2 TaqIA, rs1822497) genotypes were explored as predictors of toddlers' well-regulated behavioral and physiological responses to maternal compliance demands. Maternal sensitivity was assessed across a range of mother-child interactions when children were 6months and 1year of age (N=186), and toddler self-regulatory responses were assessed through compliance and vagal withdrawal during a toy clean-up task when children were 2years of age. Sensitivity-by-OXTR interactions suggested two diathesis-stress patterns, predicting compliance for the GG genotype group, and predicting physiological regulation for the AA/AG genotype group. A main effect for DRD2 genotype indicated that children with an A1 allele displayed less-compliant behavior in toddlerhood. These results suggest that genetic differences may contribute to variation both in risk for self-regulatory difficulties, and in relations between maternal sensitivity and children's responses to compliance demands at different levels of analysis.

G-395A polymorphism in the promoter region of the KLOTHO gene associates with frailty among the oldest-old

Frailty is characterized by a decline in physiological reserve and increased vulnerability. Previous studies have shown that KLOTHO (KL) plays a protective role in several age-related diseases. We hypothesize a probable protective effect of KL on frailty in the elderly population and included a cohort of Chinese nonagenarians and centenarians for our study. This study is part of a cross-sectional study and secondary analysis of the Project of Longevity and Aging in Dujiangyan (PLAD) study, which was conducted in Southwest China. Community-dwelling Chinese residents aged 90 years or older were included in this study. Frailty was determined using the FRAIL scale as proposed by the International Association of Nutrition and Aging. On the FRAIL scale, frailty was defined by a score of ≥3. G-395A (rs1207568) genotyping of the promoter region of the KL gene was performed using TaqMan allelic discrimination assay. A total of 632 participants (68.4% females; mean age: 93.5 ± 3.2 years) were included. KL G-395A polymorphism genotype frequencies were 1.7% AA, 25.6% GA, and 72.7% GG in our sample. GG genotype frequencies for the frailty and control groups were 83.6% and 71.2%, respectively. Frailty prevalence was significantly lower in the GA+AA group when compared to the GG genotype group (6.9% vs. 13.3%, P = 0.026). In addition, subjects with a GA+AA genotype had a significantly lower risk of frailty (odds ratio (OR): 0.47, 95% confidence interval (CI) 0.23 to 0.97, P = 0.040) compared to the GG genotype after adjusting for age, gender, education level, smoking, alcohol consumption, exercise, body mass index (BMI), cognitive impairment, and other potential factors. KL-395A allele carrying genotypes (GA and AA) is associated with a lower risk of frailty relative to GG genotypes in a sample of Chinese nonagenarians and centenarians.

The effect of the CYP2C19*2 allele on cardiovascular outcomes in patients with coronary artery stenting: a prospective study.

IntroductionThe aim of the study was to evaluate the effects of cytochrome P450 2C19*2 (CYP2C19*2) on ischemic and bleeding events in the Chinese Han population.Material and methodsPatients after coronary artery stenting were enrolled for genotyping CYP2C19*2. Platelet reactivity 4 weeks after stent implantation was compared between different genotype groups. Ischemic and bleeding events were compared after 6 months’ follow-up.ResultsA total of 255 patients were enrolled and 57.7% and 42.3% of patients presented with stable angina and acute coronary syndrome, respectively. The prevalence of homozygous (AA) and heterozygous (GA) CYP2C19*2 variants was 3.5% and 24.7% respectively, and the prevalence of wild type (GG) was 71.8%. Compared to GG and GA genotype groups, the absolute platelet activity reduction was significantly lower in AA genotype (GG 43.6 ±7.8%, GA 31.9 ±6.5%, and AA 24.8 ±5.3%, p < 0.01 for trend). After 6 months’ follow-up, 3.3%, 4.8% and 11.1% of patients experienced ischemic events in GG, GA and AA genotype groups, respectively (p = 0.003 for trend). After adjusting for traditional risk factors, AA genotype was significantly associated with ischemic events, with hazard ratio 1.19 and 95% confidence interval 1.08–1.30 (p = 0.013). Also, 2.2%, 1.6% and 0% of patients experienced bleeding events in GG, GA and AA genotype groups (p = 0.153 for trend). No independent association of CYP2C19*2 genotype and bleeding events was observed.ConclusionsGenotyping of CYP2C19*2 may be useful to guide antiplatelet treatment in the Chinese Han population. Randomized controlled trials are warranted to investigate whether genotype-guided antiplatelet treatment could reduce ischemic events.

The association study between the polymorphisms of BDNF gene and the response of citalopram antidepressant treatment

Objective To investigate the relevance of brain-derived neurotrophic factor (BDNF) gene polymorphisms and the effects of citalopram antidepressant. Methods The subjects comprised 280 patients according to the diagnostic and statistical manual of mental disorders in the fourth edition (DSM-IV) criterion for major depressive disorder (MDD). Severity of depression were assessed by 17 Hamilton depression scale (HAMD) at the baseline and 1, 2, 4, 6 weekend.Citalopram were selected for treatment.Polymerase chain reaction (PCR) and DNA sequencing analysis were used to detect the genotype of SNPs rs7124442 and rs6265 of BDNF.SPSS17.0 software was used for statistical analysis. Results (1) There were 280 patients (242 responders and 38 nonresponders; 175 remissioners and 105 nonremissioners) accomplished 6 weeks of treatment.No association was found between the polymorphisms and antidepressant drug response or remission (the reduction rate of HAMD score ≥50% was defined as response, conversely, defined as nonresponse; HAMD score more than 7 was named as remission, in contrast, named as nonremission) (P>0.05). (2) Repeated measures analysis of variance was adopted to compare the change of HAMD scores among the genotypes at different time points.There was a significant difference in rs6265 polymorphism between the GA+ AA genotype (the scores of HAMD at 2, 4, 6 weeks were(9.98±4.97), (8.02±4.50), (5.83±3.49) respectively) and the GG genotype groups (the scores of HAMD at 2, 4, 6 weeks were(11.90±6.55), (9.34±4.71), (7.07±4.28) respectively) (P=0.031). Conclusion The results suggest that BDNF rs6265 polymorphisms in part determine the antidepressant response to citalopram. Key words: Major depressive disorders; Brain-derived neurotrophic factor; Gene polymorphisms; Citalopram; Antidepressant treatment

ACAT-1 gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a case-control study.

Several studies suggest an important role of Acyl-CoA: cholesterol acyltransferase-1(ACAT-1) in the development of atherosclerosis. The aim of present study was to investigate whether there exists a possible correlation between genetic variations in ACAT-1 genes and coronary artery disease (CAD) risk. Four polymorphisms (rs1044925, rs11545566, rs12121758 and rs10913733) were finally selected and genotyped in 750 CAD patients and 580 health controls, using the improved multiplex ligation detection reaction (iMLDR) method. We found that the rs11545566 G allele was associated with a significantly elevated CAD risk [GG vs. AA: adjusted odds ratio (AOR) = 1.62, 95% confidence interval (CI) = 1.13-2.32, P = 0.008; GA/GG vs. AA: AOR = 1.67, 95% CI = 1.22-2.29, P = 0.001]. The rs10913733 G allele was also associated with a significantly elevated CAD risk (GG vs. TT: AOR = 1.57, 95% CI = 1.08-2.28, P = 0.018; GT/GG vs. TT: AOR = 1.39, 95% CI = 1.07-1.79, P = 0.013). Multivariate linear regression analysis showed that the rs11545566 polymorphism was independently associated with the Gensini scores (P = 0.005). The Gensini score of subjects in the variant GG genotype group and the GG/GA genotype group were higher than the score of subjects in the AA genotype group (32.49 ± 26.60 and 31.26 ± 26.96 vs. 23.45 ± 21.64; P = 0.001 and 0.002, respectively). Our results demonstrate that ACAT-1 rs1154556 and rs10913733 polymorphism are novel genetic factors in the development of CAD. Rs11545566 was also associated with the severity of CAD.

BclI polymorphism of the glucocorticoid receptor and adrenal crisis in primary adrenal insufficiency.

ContextPatients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at a high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR).ObjectivesTo determine if a number of intercurrent illnesses and AC are associated with the GR gene polymorphism BclI in patients with PAI and CAH.Design and patientsThis prospective, longitudinal study over 37.7 ± 10.1 months included 47 PAI and 25 CAH patients. During the study period, intercurrent illness episodes and AC were documented.ResultsThe study period covered 223 patient years in which 21 AC occurred (9.4 AC/100 pat years). There were no significant differences between BclI polymorphisms (CC (n = 29), CG (n = 34) and GG (n = 9)) regarding BMI, hydrocortisone equivalent daily dose and blood pressure. We did not find a difference in the number of intercurrent illnesses/patient year among BclI polymorphisms (CC (1.5 ± 1.4/pat year), CG (1.2 ± 1.2/pat year) and GG (1.6 ± 2.2/pat year)). The occurrence of AC was not significantly different among the homozygous (GG) genotype (32.5 AC/100 pat years), the CC genotype (6.7 AC/100 pat years) and the CG genotype (4.9 AC/100 pat years). Concomitant hypothyroidism was the highest in the GG genotype group (5/9), compared to others (CC (11/29) and CG (11/34)).ConclusionsAlthough sample sizes were relatively small and results should be interpreted with caution, this study suggests that the GR gene polymorphism BclI may not be associated with the frequencies of intercurrent illnesses and AC.

A complex association between ABCA7 genotypes and blood lipid levels in Southern Chinese Han patients of sporadic Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive decline. It can be divided into familial AD (FAD) and sporadic AD (SAD) based on the family history. Recently dysregulation of cholesterol homeostasis has been implicated in the development of late-onset AD. ATP-binding cassette transporter A7 (ABCA7) gene, regulating the transport of cholesterol, has been recently identified as a susceptible gene of AD by several large genome-wide association studies. To test the genetic effect of ABCA7 rs3764650 on blood lipid levels in Southern Chinese Han population and investigate the risk factors of SAD, a total of 118 SAD patients and 120 healthy matched controls were recruited and the genotyping in ABCA7 rs3764650 was conducted on the Sequenom MassARRAY iPLEX platform. Meanwhile, the levels of fasting lipid profile and mini-mental state examination (MMSE) scores were tested. There was significant difference in genotype distribution between SAD patients and controls (p=0.001). While the difference of ABCA7 rs3764650 allele distribution between SAD patients and controls was only significant in APOEε4-noncarriers (p=0.039). The association between blood lipid levels and ABCA7 rs3764650 genotypes was influenced by APOEε4 status. In APOEε4-noncarriers of SAD, the total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in GG genotype group were significantly lower than those in GT and TT genotype groups (all p<0.05). Whereas no significant difference of blood lipid levels was found among three genotypes in APOEε4-carriers of SAD and controls. Additionally, logistic regression analysis showed that lower high-density lipoprotein cholesterol (HDL-C) levels (p=0.015, OR=5.669) and GG genotype (p=0.013, OR=8.318) were positively associated with SAD. Our results suggest that GG genotype of ABCA7 rs3764650 was a risk factor of SAD in Southern Chinese Han population as well as lipid homeostasis.

Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically- versus genetically-driven excess fat hepatic storage

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is frequently associated with atherosclerosis. However, it is unclear whether this association is related to excess fat liver storage per se or to metabolic abnormalities that typically accompany NAFLD. To investigate this, we compared individuals with hepatic steatosis driven by metabolic disturbances to those with hepatic steatosis associated with the rs738409 GG genotype in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). MethodsCarotid intima-media thickness (CIMT), as a surrogate marker of subclinical atherosclerosis, was measured in 83 blood donors with the mutant GG genotype (group G), 100 patients with features of metabolic syndrome (MetS) but the wildtype CC genotype (group M), and 74 blood donors with the wildtype CC genotype (controls). Fatty liver was evaluated by ultrasonography and hepatic fat fraction (HFF) was measured using magnetic resonance (MRS/MRI) in 157 subjects. ResultsCompared with group G and controls, group M subjects were older and had increased adiposity indices, dyslipidemia, insulin resistance and elevated transaminase levels (all p < 0.05). They also had a more fatty liver on both ultrasonography and MRS/MRI. After adjustment for confounders (including severity of hepatic steatosis), the median CIMT in group M (0.84 [0.70–0.95] mm) was significantly greater than that in group G (0.66 [0.55–0.74] mm; p < 0.001), which was similar to that in controls (0.70 [0.64–0.81] mm). Results were similar in the subgroup evaluated using MRS/MRI. ConclusionsExcess liver fat accumulation appeared to increase the burden of subclinical atherosclerosis only when it is associated with metabolic abnormalities.