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Biomedical subjects

Jian-Qing He

Publications and source records attributed to Jian-Qing He.

11 recordsLinked to original sources
PubMed2006

Association of Hck genetic polymorphisms with gene expression and COPD.

Polymorphonuclear leukocytes (PMNs) are major effector cells in the chronic airway inflammation in chronic obstructive pulmonary disease (COPD). PMN degranulation is associated with degradation of extracellular matrix and tissue damage. Hck is an essential molecule in the signaling pathway regulating PMN degranulation. We hypothesized that polymorphisms affect the expression level of Hck, which, in turn, modulates PMN mediator release and tissue damage and influences the development of COPD. Here we systematically investigated genetic tag polymorphisms of the Hck gene, Hck mRNA and protein expression pattern in PMNs, and PMN mediator release (myeloperoxidase) in 60 healthy white subjects, and assessed their association with the use of several genetic models. The association of genetic polymorphisms with COPD-related phenotypes was determined in the lung healthy study cohort (LHS). We identified a novel 15 bp insertion/deletion polymorphism (8,656 L/S) in intron 1 of the Hck gene, which was associated with differential expression of Hck protein and PMN myeloperoxidase release. In the LHS cohort, there was significant interaction between the 8,656 L/S polymorphism and smoking on baseline lung function and 8,656 L/S was associated with bronchodilator response. These data suggest that the insertion/deletion polymorphism could be a functional polymorphism of the Hck gene, may contribute to COPD pathogenesis and modify COPD-related phenotypes.

Adult↗
PubMed2006

Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study.

BACKGROUND: Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function). METHODS: Subjects were genotyped for the alpha-defensin-1/alpha-defensin-3 copy number polymorphism and four beta-defensin-1 polymorphisms (G-20A, C-44G, G-52A and Val38Ile). RESULTS: There were no associations between individual polymorphisms or imputed haplotypes and rate of decline in lung function or susceptibility to infection. CONCLUSION: These findings suggest that, in a white population, the defensin polymorphisms tested may not be of importance in determining who develops abnormally rapid lung function decline or is susceptible to developing lower respiratory infections.

Adult↗
PubMed2006

Interferon gamma polymorphisms and their interaction with smoking are associated with lung function.

Interactions between genetic and environmental determinants are likely to be important in the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that interferon gamma (IFNG) single nucleotide polymorphisms (SNPs) and their interaction with smoking are associated with the rate of decline or level of lung function in smokers. We studied four SNPs in IFNG in 585 non-Hispanic whites (NHW) who had the fastest (n =280) or the slowest (n=305) decline of FEV(1)% predicted selected from among continuous smokers followed for 5 years in the NHLBI Lung Health Study. We also studied 1061 NHW with the lowest (n=530) or the highest (n=531) baseline lung function at the beginning of the LHS. Two SNPs were associated with baseline levels of lung function and the p values were 0.008 for +2197T/C in a dominant model and 0.002 for +5171A/G in a recessive model. However, after adjusting for confounding factors, only +5171A/G was still significant (p=0.001 for the recessive model). In addition, there was a significant genotype and smoking interaction with p=0.006 for the +5171A/G (GG vs.GA + AA) for the baseline lung function. When comparing individuals with GG versus individuals with AG + AA for low lung function, the adjusted odds ratios decreased significantly as pack-years increased. No association was found in the rate of decline study. There was an association between IFNG genotype and baseline of lung function and this association was modified by cigarette smoking.

Case-Control Studies↗
PubMed2006

[Activity and ecological distribution of actinomycetes from soil in the southeastern of Tibet].

The soil samples were collected from primeval forest, alpine meadow, marshy, grainfield and vegetable farmland ect. 9 different kinds of Vegetative type and from 2970 - 4590 altitude of southeastern of Tibet. The amount,composition, antimicrobial activity of mesophilic and psychrophilic actinomycetes and some mesophilic actinomycetes of physiological and biochemical characteristics were studied by normal methods. These actinomycetes were identified at genus level by their morphological properties. Results indicated that: (1) 9 genus of actinomycetes were isolated from soil and Actinosynnema was never reported in China. Grain field contains the largest quantity of actinomycetes. (2) Primeval forest contains the largest quantity of antimicrobal actinomycetes, so more and more antimicrobal actinomycetes information can be obtained from them. (3) The strains tested had stronger antimicrobial activity against Gram-positive bacteria than Gram-negative bacteria, had stronger antimicrobial activity against fungi than bacteria. (4) Many strains of streptomyces have some enzyme activities such as gelatin utilization, Milk-clotting enzyme etc.

Actinobacteria↗
PubMed2004

Glutathione S-transferase variants and their interaction with smoking on lung function.

We studied glutathione S-transferase (GST) polymorphisms in 1,098 whites with the lowest (n = 544, FEV(1) % predicted mean +/- SEM = 62.6 +/- 0.1) and the highest (n = 554, FEV(1) % predicted mean +/- SEM = 91.8 +/- 0.1) lung function at the beginning of the Lung Health Study. Homozygosity for GSTP1 105Val was significantly more frequent in the low- than in the high-function group (13.2 vs. 9.3%) (odds ratio = 1.69, 95% confidence interval [CI] = 1.11-2.61, p = 0.016), after adjustment for confounding variables. Subjects with 105Val homozygotes had higher rates of lung function decline in the high-function group (p = 0.017). The frequencies of GSTM1, GSTT1 null genotypes were similar between the high- and low-function groups, but subjects with the GSTT1 null genotype had a faster decline of lung function in the low-function group (p = 0.032). In addition, there was a significant interaction of GSTT1 genotype and pack-years on lung function. When comparing individuals with GSTT1 null genotype with wild type, the adjusted odds ratio was 3.49 (95% CI, 1.48-8.39, p = 0.005) in mild smokers (< or = 25 pack years). We conclude that GST genotypes are risk factors for rapid decline or low lung function in smokers with mild to moderate airflow obstruction.

Acyltransferases↗
PubMed2004

Microarray genotyping resource to determine population stratification in genetic association studies of complex disease.

We have developed a robust microarray genotyping chip that will help advance studies in genetic epidemiology. In population-based genetic association studies of complex disease, there could be hidden genetic substructure in the study populations, resulting in false-positive associations. Such population stratification may confound efforts to identify true associations between genotype/haplotype and phenotype. Methods relying on genotyping additional null single nucleotide polymorphism (SNP) markers have been proposed, such as genomic control (GC) and structured association (SA), to correct association tests for population stratification. If there is an association of a disease with null SNPs, this suggests that there is a population subset with different genetic background plus different disease susceptibility. Genotyping over 100 null SNPs in the large numbers of patient and control DNA samples that are required in genetic association studies can be prohibitively expensive. We have therefore developed and tested a resequencing chip based on arrayed primer extension (APEX) from over 2000 DNA probe features that facilitate multiple interrogations of each SNP, providing a powerful, accurate, and economical means to simultaneously determine the genotypes at 110 null SNP loci in any individual. Based on 1141 known genotypes from other research groups, our GC SNP chip has an accuracy of 98.5%, including non-calls.

Animals↗
PubMed2003

Polymorphisms in the IL13, IL13RA1, and IL4RA genes and rate of decline in lung function in smokers.

Targeted expression of interleukin (IL)-13 in the adult murine lung has been shown to cause emphysema. We hypothesized that variants in the IL13, IL13RA1, and IL4RA genes would be associated with an accelerated rate of decline of lung function among smokers. We determined the allele frequencies of five polymorphisms in the IL13, IL13RA1, and IL4RA genes in 588 continuing smokers chosen from the NHLBI Lung Health Study for having the fastest (n = 282) and slowest (n = 306) 5-yr rate of decline of lung function (mean change in FEV(1) %predicted/yr = -4.1 and +1.1, respectively). The IL4RA 551RR genotype was associated with rapid decline of lung function (odds ratio, 2.24; P = 0.043). However, none of the other four polymorphisms was associated with rate of decline in lung function. The association of 551RR with rapid decline of lung function became more significant in subjects who also had either the IL13 130RR or -1112TT genotypes. However, because multiple comparisons were made and only a few individuals had the 551RR genotype, these associations may represent type 1 error. Haplotypes consisting of alleles from the IL13 polymorphisms or from the IL4RA polymorphisms were not associated with rate of decline in lung function in smokers.

Adult↗
PubMed2002

Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers.

Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease. We hypothesized that polymorphisms of antioxidant genes glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, and heme oxygenase-1 (HMOX1) would be associated with susceptibility to accelerated decline of lung function in smokers. We genotyped 621 subjects (299 rapid decliners [change in forced expiratory volume in 1 second (DeltaFEV(1)) = -152 +/- 2.5 ml/year] and 322 nondecliners [DeltaFEV(1) = +15 +/- 1.5 ml/year]) selected from among smokers followed for 5 years in the National Heart, Lung, and Blood Institute Lung Health Study. Because genotype frequencies were different between ethnic groups, we limited the association study to 594 whites (286 rapid decliners and 308 nondecliners). None of the genotypes studied had a statistically significant effect on decline of lung function when analyzed separately. There was an association between rapid decline of lung function and presence of all three GST polymorphisms (odds ratio [OR] = 2.83; p = 0.03). A combination of a family history of chronic obstructive pulmonary disease with GSTP1 105Ile/Ile genotype was also associated with rapid decline of lung function (OR = 2.20; p = 0.01). However, due to the multiple comparisons that were made, these associations may represent type 1 error. There was no association between HMOX1 (GT)n alleles and the rate of decline in lung function in smokers.

Adult↗
PubMed2002

The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function.

The matrix metalloproteinases (MMPs) comprise a family of at least 20 proteolytic enzymes that play an essential role in tissue remodeling. MMP1 (interstitial collagenase), MMP9 (gelatinase B) and MMP12 (macrophage elastase) are thought to be important in the development of emphysema. A number of naturally occurring polymorphisms of human MMP gene promoters have been identified and found to alter transcriptional activity. Additionally, we detected a novel polymorphism in the MMP12 coding region (Asn357Ser). The aim of this study was to investigate the role of MMP polymorphisms in the development of chronic obstructive lung disease. We determined the prevalence of these polymorphisms in 590 continuing smokers chosen from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest (n = 284) and slowest (n = 306) 5 year rate of decline of lung function. Of the five polymorphisms, only G-1607GG was associated with a rate of decline in lung function. The -1607GG allele was associated with a fast rate of decline (P = 0.02) [corrected]. However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007). These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, are either causative factors in smoking-related lung injury or are in linkage disequilibrium with causative polymorphisms.

Base Sequence↗
PubMed2002

Genetic variants of the hemostatic system and development of transplant coronary artery disease.

BACKGROUND: The occurrence of coronary artery disease (CAD) after heart transplantation may represent an accelerated inflammatory and thrombotic response to coronary vascular endothelial cell injury. Several common mutations involving hemostasis and cellular adhesion proteins have been associated with genetic susceptibility to native coronary heart disease. The clinical setting of heart transplantation provides a unique opportunity to examine the relative contribution of circulating (i.e., recipient) vs local vascular (i.e., donor) hemostatic components to the occurrence of CAD. METHODS: We performed genotyping for several common hemostatic polymorphisms among 53 cardiac transplant patients and their heart donors. Patients were observed for an average of 43 months, and the presence of transplant CAD was determined by coronary angiography. RESULTS: The development of transplant CAD did not relate to recipient hemostatic genotype, but 2 donor polymorphisms (PAI-1 4G/5G and alpha(2) integrin C807T) were important predictors of transplant CAD. The risk ratio (RR) of transplant CAD associated with donor PAI-1 4G/4G genotype was 2.6 (95% confidence interval [CI] 1.1-6.2) and was modified by recipient cytomegalovirus status, hyperlipidemia, diabetes, and recipient factor XIII Val34Leu genotype. The RR of transplant CAD associated with donor alpha(2) integrin 807 T/T genotype was 7.4 (95% CI, 2.5-22.0). CONCLUSIONS: Genetic and metabolic factors contributed by both donor and recipient may interact at the level of the coronary vessel wall in the development of transplant-associated CAD, and this finding may provide additional support for the importance of local thrombotic response to endothelial injury in the pathogenesis of this disorder.

Adolescent↗