Biomedical subjects

Xiping Xu

Publications and source records attributed to Xiping Xu.

At least 37 records · Page 2Linked to original sources

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

CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population.

OBJECTIVE: There is considerable variability in the individual pharmaceutical dosages required to achieve optimal therapeutic effects, which may be due to environmental or genetic factors. The objective of this study was to test the presence of the CYP2C9*3 allelic variant in the Chinese population and to investigate the association of this variant with both metabolism and therapeutic efficacy of irbesartan on essential hypertension. METHODS: In this study, we enrolled 711 subjects from Taihu County and 376 subjects from Dongzhi County in Anhui Province, China. All subjects received a single oral dose of 150 mg irbesartan daily for 28 days. The plasma concentration of irbesartan at 24 h after dosing on the 27th day and at 6 h after dosing on the 28th day was detected using fluorescence-high-performance liquid chromatography. CYP2C9 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No CYP2C9*2 allele was found in 235 Chinese samples and was removed from further study. The mean frequency of the CYP2C9*3 allele was 3.65%, while no CYP2C9*3/*3 genotype was detected. Multiple linear regression analyses revealed that the CYP2C9*3 allele carriers had significantly higher irbesartan concentrations in plasma at 6 h (Taihu: P < 0.0001; Dongzhi: P = 0.03) and 24 h (Taihu: P < 0.0001; Dongzhi: P = 0.00013) after dosing. No significant association was found between the CYP2C9*3 allelic variant and the therapeutic effect of irbesartan on essential hypertension. CONCLUSION: Our study suggests that the CYP2C9*3 plays an important role in the metabolism of irbesartan and/or is in linkage disequilibrium with another potential CYP2C9 allele, both of which possibly modify the pharmacokinetics of irbesartan.

Administration, Oral↗

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

Preconception serum DDT and pregnancy loss: a prospective study using a biomarker of pregnancy.

Previous studies of pregnancy losses and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) were limited because they did not include losses prior to clinical detection of pregnancy and because exposures were measured after the pregnancies of interest. The authors examined the association of preconception serum total DDT (sum of DDT isomers and metabolites) concentration and subsequent pregnancy losses in 388 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. There were 128 (26%) early pregnancy losses in 500 conceptions and 36 (10%) spontaneous abortions in 372 clinical pregnancies. Subjects were grouped in tertiles by preconception serum total DDT concentration (group 1: 5.5-22.9 ng/g; group 2: 23.0-36.5 ng/g; group 3: 36.6-113.3 ng/g). Compared with group 1, group 2 had adjusted relative odds of early pregnancy losses of 1.23 (95% confidence interval (CI): 0.72, 2.10), and group 3 had adjusted odds of 2.12 (95% CI: 1.26, 3.57). The relative odds of early pregnancy losses associated with a 10-ng/g increase in serum total DDT were 1.17 (95% CI: 1.05, 1.29). The small number of spontaneous abortions following clinical detection of pregnancy were not associated with serum total DDT. In this population, there was a positive, monotonic, exposure-response association between preconception serum total DDT and the risk of subsequent early pregnancy losses.

Abortion, Spontaneous↗

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

Familial aggregation of airway responsiveness: a community-based study.

PURPOSE: We investigated the familial aggregation of airway hyper-responsiveness (AHR) to methacoline among randomly chosen families in a rural community in Anqing, China. METHODS: Airway responsiveness (AR) to methacoline and related risk factors were assessed in each subject. We first modeled the within family correlation in AR and demonstrated the familial aggregation of this trait. Furthermore, we examined the effect size (e.g., odds ratio, OR) of this correlation in a "subsequent offspring model." RESULTS: The correlation coefficient is significantly positive for parent-offspring and offspring-offspring pairs, but not significant in father-mother pairs, suggesting a genetic component. The strength of the relationships is in the order of father-offspring < mother-offspring < offspring-offspring. The OR of a positive AHR test for subsequent offspring who had mothers and an eldest sibling with positive AHR is 4.12 (95% CI, 1.72-9.87), compared with subsequent offspring whose mother and eldest sibling were negative in the test. CONCLUSION: Our study supports a familial clustering of AHR in a Chinese population, which points to a role for genetic factors.

Adolescent↗

PubMed2005

Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension.

BACKGROUND: Individual variations in the pharmacokinetics and pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension. OBJECTIVE: This study examined the relationship between ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension. METHODS: Patients with essential hypertension who had taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP) <90 mm Hg (DBP analysis), a systolic BP (SBP) <140 mm Hg (SBP analysis), and a DBP <90 mm Hg and SBP <140 mm Hg (DBP and SBP analysis). RESULTS: The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: -2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: -12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBP > or =100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: -5.7 [1.4] mm Hg; P < 0.001) and SBP compared with those with the Val/Val genotype and a baseline DBP > or =100 mm Hg (adjusted regression coefficient: -9.8 [2.9] mm Hg; P < 0.001). CONCLUSION: The findings of this study suggest that in these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.

Adult↗

PubMed2005

Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects.

BACKGROUND: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha1A-adrenergic receptor (alpha1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level. METHODS: A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. RESULTS: BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha1A-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours. CONCLUSION: Our data suggest that the alpha1A-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha1A-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.

Aged↗

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

Body mass index and serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane in nulliparous Chinese women.

BACKGROUND: Basic health indicators, such as body mass index (BMI), have been associated with serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane/1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT/DDE) levels; however, both positive and inverse associations of BMI with serum DDT/DDE have been reported. Given the association of BMI with a number of outcomes, it may confound studies of DDT/DDE-associated health effects. We investigated the relationship of BMI with serum DDT/DDE accounting for other determinants of exposure among women with relatively recent environmental exposures to DDT. METHODS: Serum DDT/DDE was analyzed in 466 nonsmoking, nulliparous women recruited from Anhui province in China between 1996 and 1998 as part of a reproductive health study of textile workers. The women in the sample were born between 1963 and 1977, 8 to 21 years before China's 1984 DDT ban. We used multivariate linear regression to investigate associations of BMI, age, and birth year with serum DDT/DDE. RESULTS: Mean (SD) serum total DDT concentration was 32 ng/g (17.8 ng/g). Birth year showed an inverse relationship with serum DDT independent of age. Despite limited variability in BMI, there was a consistent inverse relationship between BMI and serum DDT. Specifically, each kg/m(2) increase in BMI was associated with a -1.34 ng/g (95% confidence interval, -2.12 to -0.56 ng/g) decrease in serum total DDT. CONCLUSIONS: There were high total DDT levels in this sample of nulliparous Chinese women relative to Western populations, birth year was more strongly associated with serum DDT than age, and BMI was inversely related to serum DDT in this study.

Adult↗

PubMed2005

Effect of environmental tobacco smoke on levels of urinary hormone markers.

Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.

Adult↗

PubMed2005

Association of cigarette smoking with steady-state plasma concentration of irbesartan in male Chinese with hypertension.

Previous studies suggested that cigarette smoking, being highly prevalent in many countries, is an important environmental factor that contributes to interindividual variations in response to certain medications. To investigate the possible interactions between irbesartan (a commonly used angiotensin II type 1 receptor antagonist) and cigarette smoking, we recruited 491 male patients with essential hypertension from two rural districts of China. All subjects were treated with irbesartan (150 mg/day) for 28 days, and the steady-state plasma concentrations of irbesartan 24 h after the dose of day 27 (the trough level) and 6 h after the dose of day 28 were determined using prevalidated high-performance liquid chromatography (HPLC)-fluorescence method. Multiple linear regression was used to analyze the effect of smoking on the steady-state plasma concentrations of irbesartan, with potential confounding factors adjusted. The results showed that current smokers had significantly higher average steady-state trough plasma level of irbesartan than that of the nonsmokers and former smokers. The finding was still valid when subjects from the two different districts were separately analyzed. The stratified analysis according to age suggested that the effect of increasing irbesartan concentration by current cigarette smoking in the elderly patients was stronger than that in adults. The metabolism of irbesartan in current smokers was slower compared to that in nonsmokers and former smokers. In summary, the present study showed significant associations between current cigarette smoking and an increased steady-state trough plasma concentration of irbesartan in a male Chinese population with hypertension. The metabolic rate of irbesartan in current smokers was slower than those in nonsmokers and former smokers.

Antihypertensive Agents↗

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

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↗

PubMed2004

Paternal smoking and pregnancy loss: a prospective study using a biomarker of pregnancy.

Results of studies on paternal smoking and spontaneous abortions have been inconsistent. The authors examined the effect of paternal smoking on the risk of pregnancy loss in a prospective cohort of 526 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. Subjects were grouped by the number of cigarettes that husbands reported smoking daily: nonsmokers (group 1, n = 216), fewer than 20 cigarettes (group 2, n = 239), and 20 or more cigarettes (group 3, n = 71). Compared with that for group 1, the adjusted odds ratio of early pregnancy loss of any conception for group 2 was 1.04 (95% confidence interval (CI): 0.67, 1.63) and for group 3 was 1.81 (95% CI: 1.00, 3.29). The adjusted hazard ratio of conception for group 2 was 0.90 (95% CI: 0.70, 1.18) and for group 3 was 0.96 (95% CI: 0.66, 1.39), while the adjusted hazard ratio of clinical pregnancy for group 2 was 0.93 (95% CI: 0.72, 1.20) and for group 3 was 0.78 (95% CI: 0.55, 1.12). The authors conclude that heavy paternal smoking increased the risk of early pregnancy loss through maternal and/or paternal exposure.

Abortion, Spontaneous↗