Biomedical subjects

Tianhua Niu

Publications and source records attributed to Tianhua Niu.

At least 19 recordsLinked to original sources

PubMed2007

Large-scale genome-wide linkage analysis for loci linked to BMD at different skeletal sites in extreme selected sibships.

UNLABELLED: Few genome-wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome-wide scan involving 3093 adult siblings with at least one sib-pair extremely concordant or discordant for hip BMD. Our results indicated four genome-wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance. INTRODUCTION: The genetic basis for osteoporosis has been firmly established, but efforts to identify genes associated with this complex trait have been incomplete, especially in Asian populations. The purpose of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese population. MATERIALS AND METHODS: We performed a genome-wide scan involving 3093 siblings 25-64 years of age from 941 families, with at least one sib-pair extreme concordant or discordant for total hip BMD from a large community-based cohort (n = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals adjusted for age, height, weight, occupation, cigarette smoking, physical activity, and alcohol consumption using the revised Haseman-Elston regression-based linkage model. RESULTS: Our results revealed significant QTLs on chromosome 7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage analysis further revealed a significant QTL for lumbar spine BMD on chromosome 13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral neck, and lumbar spine BMD), an additional significant QTL was found at chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study overlapped with major QTLs reported by other studies. CONCLUSIONS: This study reveals four novel QTLs in a Chinese population and suggests that BMD at different skeletal sites may also share common genetic determinants.

Asian People↗

PubMed2006

A coalescence-guided hierarchical Bayesian method for haplotype inference.

Haplotype inference from phase-ambiguous multilocus genotype data is an important task for both disease-gene mapping and studies of human evolution. We report a novel haplotype-inference method based on a coalescence-guided hierarchical Bayes model. In this model, a hierarchical structure is imposed on the prior haplotype frequency distributions to capture the similarities among modern-day haplotypes attributable to their common ancestry. As a consequence, the model both allows distinct haplotypes to have different a priori probabilities according to the inferred hierarchical ancestral structure and results in a proper joint posterior distribution for all the parameters of interest. A Markov chain-Monte Carlo scheme is designed to draw from this posterior distribution. By using coalescence-based simulation and empirically generated data sets (Whitehead Institute's inflammatory bowel disease data sets and HapMap data sets), we demonstrate the merits of the new method in comparison with HAPLOTYPER and PHASE, with or without the presence of recombination hotspots and missing genotypes.

Algorithms↗

PubMed2006

Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia.

OBJECTIVE: Renin-angiotensin System is essential for the homeostasis of blood pressure in humans. The roles of renin-angiotensin system gene polymorphisms including angiotensinogen, angiotensin-converting enzyme, renin and angiotensin II receptor, type 1 genes in the pathogenesis of preeclampsia have been extensively studied, but most association studies produced either negative or inconsistent results. Prolylcarboxypeptidase encodes a lysosomal enzyme and is a regulator for both renin-angiotensin system and the kallikrein-kinin system. There is no published study on prolylcarboxypeptidase gene and preeclampsia. STUDY DESIGN: We investigated the independent and joint association of five polymorphisms in angiotensinogen, angiotensin-converting enzyme, and prolylcarboxypeptidase gene and chronic hypertension with the risk of preeclampsia in 125 preeclamptic and 1040 non-preeclamptic black women enrolled at the Boston Medical Center. We used logistic regression models to estimate the odds ratios of risk for preeclampsia associated with each gene polymorphism and its joint association with chronic hypertension. RESULTS: No association was found in four polymorphisms in angiotensinogen and angiotensin-converting enzyme. Prolylcarboxypeptidase E112D (rs2298668) D allele along and jointly with chronic hypertension were associated with a significantly increased risk of preeclampsia. Compared to women with homozygous EE genotype and without chronic hypertension, higher risks of preeclampsia were observed in DD women without chronic hypertension (OR = 3.7, 95% CI, 1.2 - 12.4) and EE women with chronic hypertension (OR = 9.1, 95% CI: 4.7 - 17.6). Women with both D allele and chronic hypertension had the highest risk (OR = 158, 95% CI, 25-infinite). This finding was validated in an independent sample of 1,015 non-black women. We further compared the prolylcarboxypeptidase transcript levels in peripheral blood cells of 23 preeclamptic (30% with chronic hypertension) and 51 non-preeclamptic (6% with chronic hypertension) women 2 - 3 days after delivery. The PRCP transcript levels were lower in ED/DD women than in EE woman (P = .03) and lower in preeclamptic women than in non-preeclamptic women (P = .007). CONCLUSION: Our data showed that prolylcarboxypeptidase D allele coupled with chronic hypertension was associated with a significantly increased risk of preeclampsia in both black and non-black women. Gene expression assays lent further support for the functional significance of prolylcarboxypeptidase in the etiology of preeclampsia.

Adult↗

PubMed2006

Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women.

BACKGROUND: Higher fat mass may be an independent risk factor for osteoporosis and osteoporotic fractures. OBJECTIVE: We aimed to determine the independent contribution of fat mass to osteoporosis and to estimate the risk of osteoporotic fractures in relation to body weight, lean mass, and other confounders. DESIGN: This was a community-based, cross-sectional study of 7137 men, 4585 premenopausal women, and 2248 postmenopausal women aged 25-64 y. Total-body and hip bone mineral content (BMC) and bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry. Serum lipids were measured. Sex- and menopause-specific multiple generalized linear models were applied. RESULTS: Across 5-kg strata of body weight, fat mass was significantly inversely associated with BMC in the whole body and total hip. When we compared the highest quartile with the lowest quartile of percentage fat mass in men, premenopausal women, and postmenopausal women, the adjusted odds ratios (95% CIs) of osteoporosis defined by hip BMD were 5.2 (2.1, 13.2), 5.0 (1.7, 15.1), and 6.9 (4.3, 11.2), respectively. Significant linear trends existed for higher risks of osteoporosis, osteopenia, and nonspine fractures with higher percentage fat mass. Significant negative relations were found between whole-body BMC and cholesterol, triacylglycerol, LDL, and the ratio of HDL to LDL in all groups. CONCLUSIONS: Risks of osteoporosis, osteopenia, and nonspine fractures were significantly higher for subjects with higher percentage body fat independent of body weight, physical activity, and age. Thus, fat mass has a negative effect on bone mass in contrast with the positive effect of weight-bearing itself.

Absorptiometry, Photon↗

PubMed2005

Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men.

In order to assess the contribution of polymorphisms in the RANKL (TNFSF11), RANK (TNFRSF11A) and OPG (TNFRSF11B) genes to variations in bone mineral density (BMD), a population-based cohort with 1,120 extreme low hip BMD cases or extreme high hip BMD controls was genotyped on five SNPs. We further explored the associations between these genetic variations and forearm BMDs by genotyping 266 offspring and 309 available parents from 160 nuclear families. A family-based association test was used. Significantly positive associations were found for A163G polymorphisms in the promoter regions of the OPG gene, a missense substitution in exon 7 (Ala192Val) of the RANK gene and rs9594782 SNP in the 5' UTR of the RANKL gene with BMD in men only. Men with TC/CC genotypes of the rs9594782 SNP had a 2.1 times higher risk of extremely low hip BMD (P = 0.004), and lower whole body BMD (P < 0.001). Subjects with the TC genotype of the Ala192Val polymorphism had a 40% reduced risk of having extremely low hip BMD (P < 0.01), and higher whole body BMD (P < 0.01). Subjects with the GG genotype of the A163G polymorphism had a 70% reduced risk of having extremely low hip BMD (P < 0.05), and higher whole body BMD (P < 0.01). Significant gene-gene interactions were also observed among the OPG, RANK and RANKL genes. Our findings suggest that genetic variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are strongly associated with BMD at different skeletal sites in adult men, but not in women.

Adult↗

PubMed2005

The insulin-like growth factor-I gene and osteoporosis: a critical appraisal.

Osteoporosis, a disorder of skeletal fragility, is common in the elderly, and its prevalence is increasing as more individuals with low bone mineral density (BMD), the strongest predictor of fracture risk, are detected. Previous basic and clinical studies imply there is a significant role for insulin-like growth factor-I (IGF-I) in determining BMD. Recently, polymorphisms upstream of the P1 promoter region of the human IGF-I gene have been found to be associated with serum levels of IGF-I, BMD and fracture risk in various ethnic groups. Multiple quantitative trait loci (QTLs) have been identified that underlie serum IGF-I in a mouse intercross between two inbred strains. The most promising QTL on mouse chromosome 6 has provided clues for unraveling the molecular mechanisms that regulate osteoblast differentiation. Genomic engineering resulting in IGF-I deficient mice, and mice with targeted over-expression of IGF-I reinforce the essential role of IGF-I in bone development at both the embryonic and postnatal stages. Thus, it is apparent that significant new insights into the role of the IGF-I gene in bone remodeling occur through several distinct mechanisms: (1) the skeletal IGF regulatory system; (2) the systemic growth hormone/IGF-I axis; (3) parathyroid hormone signaling; (4) sex steroids; and (5) the OPG/RANKL/RANK cytokine system. Molecular dissection of the IGF regulatory system and its signaling pathway in bone may reveal novel therapeutic targets for the treatment of osteoporosis.

Animals↗

PubMed2005

Familial aggregation of bone mineral density and bone mineral content in a Chinese population.

Familial aggregation of bone mineral density (BMD) and bone mineral content (BMC) has been shown in twin and familial studies, but most sample sizes were small. We here report a large familial aggregation study in a Chinese population. A total of 13,973 siblings aged 25-64 years from 3,882 families were enrolled from Anhui, China. We assessed the whole-body, hip and lumbar spine BMD and BMC by dual-energy X-ray absorptiometry (DXA). Intra-class correlation coefficients of BMD and BMC between siblings varied among different skeletal sites and between different age groups of male sib-pairs and premenopausal and postmenopausal female sib-pairs, with a range of 0.228 to 0.397. The sibling recurrence risk ratio (lambdas) of osteoporosis was 2.6 in our population. We also evaluated the joint association of the BMD values of the first siblings and the second siblings with the risk of low BMD (defined as less than the 10th percentile of the same group population) of their younger siblings. If both the first and second siblings' BMDs were in the lowest tertile, the odd ratios (ORs) of low BMD in their subsequent siblings were 8.32 [95% confidence interval (CI) 5.59-12.39)], 8.71 (95% CI 5.74-13.22) and 5.90 (95% CI 3.57-9.76) for total body, total hip and lumbar spine, respectively. This study demonstrates a significant familial aggregation of BMD and BMC in a large sample of rural Chinese adults.

Absorptiometry, Photon↗

PubMed2005

SNPHunter: a bioinformatic software for single nucleotide polymorphism data acquisition and management.

BACKGROUND: Single nucleotide polymorphisms (SNPs) provide an important tool in pinpointing susceptibility genes for complex diseases and in unveiling human molecular evolution. Selection and retrieval of an optimal SNP set from publicly available databases have emerged as the foremost bottlenecks in designing large-scale linkage disequilibrium studies, particularly in case-control settings. RESULTS: We describe the architectural structure and implementations of a novel software program, SNPHunter, which allows for both ad hoc-mode and batch-mode SNP search, automatic SNP filtering, and retrieval of SNP data, including physical position, function class, flanking sequences at user-defined lengths, and heterozygosity from NCBI dbSNP. The SNP data extracted from dbSNP via SNPHunter can be exported and saved in plain text format for further down-stream analyses. As an illustration, we applied SNPHunter for selecting SNPs for 10 major candidate genes for type 2 diabetes, including CAPN10, FABP4, IL6, NOS3, PPARG, TNF, UCP2, CRP, ESR1, and AR. CONCLUSION: SNPHunter constitutes an efficient and user-friendly tool for SNP screening, selection, and acquisition. The executable and user's manual are available at http://www.hsph.harvard.edu/ppg/software.htm

Algorithms↗

PubMed2005

Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness.

Airway hyperresponsiveness (AHR) is one of the major clinical symptoms and intermediate phenotypes of asthma. A recent genome-wide search for asthma quantitative trait loci has revealed a significant linkage signal between a p-terminal region of chromosome 2 and AHR. Thus, the gene encoding the potassium voltage-gated channel delayed-rectifier protein S3 (KCNS3) in this region is considered a positional candidate for asthma. We have evaluated a total of 12 single-nucleotide polymorphisms (SNPs) of the KCNS3 gene in a validation panel of 48 lymphoblastoid cell line DNA samples of Chinese origin. Three SNPs were found to be polymorphic and were tested. Two independent sets (an initial screening set and a replication set) of cases and controls from the original linkage study sample were collected. In the initial screening set, two SNPs (rs1031771 and rs1031772) showed suggestive association and were further confirmed by the replication set. In combined single-SNP analysis, the rs1031771 G allele (odds ratio=1.42, P=0.006) and rs1031772 T allele (odds ratio=1.40, P=0.018) were associated with a significantly higher risk of AHR. Haplotype analysis also detected significant association (P=0.006). Our findings suggest that SNPs located at the 3' downstream region of KCNS3 have a significant role in the etiology of AHR.

Adult↗

PubMed2005

A sparse marker extension tree algorithm for selecting the best set of haplotype tagging single nucleotide polymorphisms.

Single nucleotide polymorphisms (SNPs) play a central role in the identification of susceptibility genes for common diseases. Recent empirical studies on human genome have revealed block-like structures, and each block contains a set of haplotype tagging SNPs (htSNPs) that capture a large fraction of the haplotype diversity. Herein, we present an innovative sparse marker extension tree (SMET) algorithm to select optimal htSNP set(s). SMET reduces the search space considerably (compared to full enumeration strategy), and therefore improves computing efficiency. We tested this algorithm on several datasets at three different genomic scales: (1) gene-wide (NOS3, CRP, IL6 PPARA, and TNF), (2) region-wide (a Whitehead Institute inflammatory bowel disease dataset and a UK Graves' disease dataset), and (3) chromosome-wide (chromosome 22) levels. SMET offers geneticists with greater flexibilities in SNP tagging than lossless methods with adjustable haplotype diversity coverage (phi). In simulation studies, we found that (1) an initial sample size of 50 individuals (100 chromosomes) or more is needed for htSNP selection; (2) the SNP tagging strategy is considerably more efficient when the underlying block structure is taken into account; and (3) htSNP sets at 80-90% phi are more cost-effective than the lossless sets in term of relative power, relative risk ratio estimation, and genotyping efforts. Our study suggests that the novel SMET algorithm is a valuable tool for association tests.

Algorithms↗

PubMed2005

Associations of baseline blood pressure levels and efficacy of Benazepril treatment with interaction of alpha-adducin and ACE gene polymorphisms in hypertensives.

The molecular mechanisms underlying essential hypertension are not fully elucidated. Although Benazepril is being widely used in antihypertensive medication, the agent is efficacious in only a portion of hypertensive patients. To evaluate the interaction of alpha-adducin gene Gly460Trp and angiotensin I-converting enzyme (ACE) gene I/D polymorphisms in regard to baseline blood pressure (BP) levels and the reductions of blood pressures after Benazepril treatment, we conducted an investigation of 954 Chinese hypertensive patients in Anhui province, China. We found that compared with the baseline systolic BP (SBP) of subjects with one ACE I allele and one alpha-adducin Trp allele, the baseline SBP of those with ACE DD and alpha-adducin Gly/Gly genotypes was significantly higher [Crude: beta(SE) = 7.83(3.09), p = .01; Adjusted: beta(SE) = 5.83(2.83), p = .04]. However, no associations were found between the interaction of ACE I/D and alpha-adducin Gly460Trp polymorphisms and the baseline diastolic BP or the BP response to Benazepril treatment. Our results suggested that the interaction effect of alpha-adducin Gly460Trp and ACE I/D polymorphisms might play a significant role in regulating baseline BP but not BP response to Benazepril.

Adult↗

PubMed2005

A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients--a family-based association study.

Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.

Adult↗

PubMed2005

PON1 polymorphism, diabetes mellitus, obesity, and risk of myocardial infarction: Modifying effect of diabetes mellitus and obesity on the association between PON1 polymorphism and myocardial infarction.

PURPOSE: Previous studies on PON1 gene polymorphism and the risk of coronary atherosclerotic diseases have been inconsistent. This may be in part due to population difference in prevalence of high oxidative stress and its modifying effect on the association. Diabetes and obesity are two major risk factors of myocardial infarction (MI) and associated with high oxidative stress. We investigated the association between PON1 Q192R polymorphism and the risk of myocardial infarction (MI) and in particular, whether the association can be modified by diabetes mellitus (DM) and obesity. METHODS: We conducted a case-control study, including 154 MI cases and 154 controls enrolled in Beijing, China. Epidemiological and clinical data and PON1 Q192R genotype were obtained from each subject. RESULTS: Without considering the modifying effect of DM and obesity, PON1 Q192R polymorphism was not associated with MI. When simultaneously examining the joint association of this polymorphism, DM, and obesity with MI, as compared to subjects with QQ genotypes and without DM and obesity, subjects with QR/RR genotypes and with either DM or obesity had significantly higher risk of MI (OR = 3.6, 95% CI: 1.5-8.7). CONCLUSION: Our data suggest that PON1 Q192R polymorphism was not independently associated with MI but further increased the risk of MI among the subjects with DM, obesity, or both, the conditions associated with high oxidative stress.

Aryldialkylphosphatase↗

PubMed2005

An expectation-maximization-likelihood-ratio test for handling missing data: application in experimental crosses.

The mapping of quantitative trait loci (QTL) is an important research question in animal and human studies. Missing data are common in such study settings, and ignoring such missing data may result in biased estimates of the genotypic effect and thus may eventually lead to errant results and incorrect inferences. In this article, we developed an expectation-maximization (EM)-likelihood-ratio test (LRT) in QTL mapping. Simulation studies based on two different types of phylogenetic models revealed that the EM-LRT, a statistical technique that uses EM-based parameter estimates in the presence of missing data, offers a greater statistical power compared with the ordinary analysis-of-variance (ANOVA)-based test, which discards incomplete data. We applied both the EM-LRT and the ANOVA-based test in a real data set collected from F2 intercross studies of inbred mouse strains. It was found that the EM-LRT makes an optimal use of the observed data and its advantages over the ANOVA F-test are more pronounced when more missing data are present. The EM-LRT method may have important implications in QTL mapping in experimental crosses.

Algorithms↗

PubMed2004

Genetic variants of the lipoprotein lipase gene and myocardial infarction in the Central Valley of Costa Rica.

To assess common variants of the LPL gene that could influence susceptibility to myocardial infarction (MI), we assessed three functional single-nucleotide polymorphisms (SNPs), D9N, N291S, and S447X, in 1,321 survivors of a first acute MI and 1,321 population-based controls, matched for age, gender, and area of residence, all living in the Central Valley of Costa Rica. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI). The frequency of the X447 mutant allele was significantly lower in cases than in controls (6.2% vs. 7.6%; P < 0.01), whereas no association with MI was found for D9N or N291S. The OR (95% CI) for carriers vs. noncarriers of the X447 allele was 0.80 (0.63-1.01); when considering the haplotype that contained X447 and normal alleles of D9N and N291S, the OR (95% CI) was 0.66 (0.48-0.91). Twelve other SNPs were assessed in a subgroup of the population, of which the four functional SNPs were found to be monomorphic, and no correlation with MI was observed for the other eight neutral SNPs. The X447 mutant allele of the LPL gene may protect from MI risk, although this effect is small.

Adult↗

PubMed2004

SNPicker: a graphical tool for primer picking in designing mutagenic endonuclease restriction assays.

Simple, low-cost and accurate genotyping methods for single nucleotide polymorphisms (SNPs) are in high demand in the post-genome-sequencing era. We present a graphical tool called SNPicker, implemented in Java, which significantly facilitates the design of mutagenic endonuclease restriction assays. SNPicker uses the online NEB REBASE to automatically scan for all possible designs of mutagenic primers that can facilitate the picking of mismatched PCR primers to artificially introduce or abolish a restriction site at the target SNP site. We successfully applied SNPicker in designing endonuclease restriction assays for 14 SNPs for the MTHFR gene, the Coagulation Factor II gene and the Coagulation Factor V gene. The SNP assays designed using SNPicker were cross-validated using the MassARRAY technology.

Computer Graphics↗

PubMed2004

A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men.

Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.

Adult↗

PubMed2004

D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients.

Individual variation in drug response is considered to have multiple origins arising from interactions among susceptible genes and environmental factors. A total of 726 hypertensive patients who took benazepril 10 mg once a day for 15 days and their families from Huoqiu county of Anhui Province, China, were used to study the association between D919G polymorphism of methionine synthase (MTR) gene and the antihypertensive effect of this angiotensin-converting enzyme inhibitor. Compared to the 919D allele, both population-based ( P=0.010) and family-based association tests (additive model P=0.018, dominant model P=0.025) demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. Our finding suggests that the D919G polymorphism of the MTR gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril therapy in hypertensive patients of Anhui Province, China.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗