RQ Genotype Research Articles

Interleukin-4 and Interleukin-13 Gene Polymorphisms in Children With Idiopathic Nephrotic Syndrome.

Background: Idiopathic Nephrotic syndrome (INS) is an immune-mediated disease in which a number of cytokines, including IL-4 and IL-13, have been implicated in the pathogenesis. Cytokine gene polymorphisms might affect their levels and activity. Therefore, may affect INS susceptibility and response to treatment. The aim of the study was to determine the association of IL-4 and IL-13 gene polymorphisms and INS susceptibility and their effects on steroid responsiveness in children.Methods: The polymorphisms in IL-4 and IL-13 genes were detected by PCR-RFLP in 155 INS patients and 64 controls.Results: A total of 132 steroid-sensitive (SS) and 23 steroid resistance (SR) INS patients; mean age 7.3 ± 4.0 years, were included. Male: Female ratio was 2:1. No significant statistical differences were detected in the frequency of CC, CT, and TT genotypes of IL-4 gene compared to controls (P = 0.57, 0.61, and 1.00, respectively). There was no significant difference in the T and C-allele frequencies, in SS and SR subgroups. Analysis of IL-13 gene polymorphism also did not show significant statistical differences in the frequency of QQ, RQ, and RR genotypes compared to controls (P = 0.74, 1.00, and 0.68, respectively). No significant difference was found in the Q and R-allele frequency. However, the heterozygous RQ genotype of the IL13 gene was significantly higher in SS INS patients compared to the SR INS cases (P = 0.04).Conclusion: Our findings did not show an association between IL-4 and IL-13 gene polymorphisms and INS susceptibility. However, IL-13 RQ genotype was expressed more in children with INS who are steroid sensitive.

Genotype-phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease

Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed ignificantly across R353Q genotype (P < 0.0001). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively (P < 0.0001). F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score -1.82; P = 0.002). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506-2.850) and 2.472 (95% c.i. = 1.679-3.641), espectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.

Matrix metalloproteinase-9-1562C&gt;T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer

To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population. Genotyping of MMP-9-1562C>T and 279R>Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). The distribution of MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph node metastasis of CRC was increased in patients with the -1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP-9 279RR + RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102; 95% CI = 0.013-0.812; P = 0.012). Our results indicated that the MMP-9-1562C>T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.

Association of beta-fibrinogen and factor VII polymorphism with plasma fibrinogen and factor VII levels, and no association of PAI-1 polymorphism with plasma PAI-1 levels in hemodialysis patients.

Recent studies have stressed the roles of genetic factors on the plasma levels of hemostatic markers and on cardiovascular complications. We investigated the association of DNA polymorphisms for beta-fibrinogen, factor VII, and PAI-1 with plasma levels of these factors and with ischemic heart disease (IHD) and cerebral infarction (CI) in patients undergoing hemodialysis (HD). beta-fibrinogen G/A-455, factor VII R353Q and PAI-1 4G/5G polymorphisms were determined by PCR-RFLP in 149 HD patients and in 100 controls. The plasma levels of fibrinogen, factor VII and PAI-1 were also measured. The allele frequencies and the genotype frequencies of these 3 polymorphisms were not different between HD patients and controls. In HD patients, plasma fibrinogen levels were significantly lower in the GG genotype than in the GA genotype, and plasma factor VII activity was significantly higher in the RR genotype than in the RQ genotype. Multiple regression analysis disclosed that CRP and beta-fibrinogen polymorphism were the significant determinants of fibrinogen levels. Plasma PAI-1 levels were not different among the 3 genotypes. The frequency of the A-455 allele was significantly higher in HD patients with CI than in those without CI, and the genotype distribution for beta-fibrinogen differed significantly between the 2 groups. Between the same 2 groups, however, significant differences were found neither in the frequency of the 353Q or 4G allele nor in the genotype distribution for factor VII and PAI-1. No significant differences in the frequency of the G-455, 353Q or 4G alleles, or in the genotype distribution for beta-fibrinogen, factor VII and PAI-1 were observed between patients with IHD and those without IHD. Multiple logistic regression analysis demonstrated that neither polymorphism was associated with CI or IHD. In HD patients, beta-fibrinogen and factor VII polymorphisms affected plasma levels of fibrinogen and factor VII, respectively. Beta-fibrinogen polymorphism was not an independent but a possible risk factor for CI in HD patients. Further study will be needed to confirm the precise role of 5-fibrinogen polymorphisms in the pathogenesis of CI in HD patients.

Postprandial response of activated factor VII in elderly women depends on the R353Q polymorphism

Activated factor VII (FVIIa) is a very potent coagulant and may be a key determinant of the outcome of a cardiovascular event. The main determinants of FVIIa are the R353Q polymorphism and dietary fat intake, which may have an interactive effect. The objective was to investigate whether the response of FVIIa to a fat-rich breakfast varies across genotypes of the R353Q polymorphism. Ninety-one apparently healthy elderly women (>60 y of age), 56 with the RR genotype and 35 with the RQ or QQ genotype, participated in a randomized, controlled crossover study. Subjects received 5 breakfasts, each on a separate day: 1 low-fat control breakfast and 4 high-fat test breakfasts. Blood samples were taken for measurement of FVIIa at 0800 before each breakfast (fasting) and at 1300 and 1500. The mean (+/-SD) fasting FVIIa concentration was 93.3 +/- 26.7 U/L in women with the RR genotype, 49.3 +/- 19.1 U/L in those with the RQ genotype and 39.5 +/- 17.2 U/L in those with the QQ genotype. The mean absolute response to all 4 test breakfasts was 37.0 U/L in those with the RR genotype and 16. 1 U/L in those carrying the Q allele (P < 0.001 for difference). Likewise, the FVIIa response relative to fasting FVIIa was significantly higher in women homozygous for the R allele. This observation may indicate a considerable difference in cardiovascular risk between genotype groups as a result of an increase in FVIIa after a fat-rich diet.

Dietary oleic and palmitic acids and postprandial factor VII in middle-aged men heterozygous and homozygous for factor VII R353Q polymorphism

The R353Q genotype is a major determinant of factor VII coagulant (FVIIc) activity, which is associated with an increased risk of ischemic heart disease (IHD) and elevated plasma triacylglycerol concentrations. The objectives were to 1) compare the effects of meals rich in palmitate or oleate with those of a meal low in fat on FVIIc in subjects with moderately elevated plasma nonfasting triacylglycerol concentrations and 2) determine whether the postprandial increase in FVIIc induced by dietary oleate differs in carriers of the Q allele. Fifty-two men aged >52 y with nonfasting plasma triacylglycerol concentrations between 2 and 5.5 mmol/L were randomly assigned to receive isoenergetic (5.1 MJ) meals providing 50 g high-oleate or high-palmitate oils or a low-fat meal providing 15 g high-oleate oil. In a second study, 17 men aged >52 y who were heterozygous for factor VII R353Q polymorphism were age-matched with subjects homozygous for the R allele and their responses to a 50-g, high-oleate meal were measured. FVIIc decreased by 11% after the low-fat meal. FVIIc increased by 9% and FVIIa (the activated form of FVII) increased by 55% after the high-oleate meal, whereas FVIIc did not change but FVIIa increased by 25% after the high-palmitate meal. Fasting FVIIc and FVIIa concentrations were 24% and 48% lower, respectively, in men with the RQ genotype than in men with the RR genotype but increased postprandially in both groups with no evidence of a genotype interaction. A high-fat meal rich in oleate increases FVIIa, whereas a low-fat meal does not, in men at high risk of IHD, independent of R353Q genotype.

Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction.

High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established. We performed a case-control study of 165 patients with familial myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VII gene were studied. Factor VII clotting activity and antigen levels were also measured. Patients with the QQ or H7H7 genotype had a decreased risk of myocardial infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34). Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels.