Frequency Of BB Genotype Research Articles

Natural Killer Cell Immunoglobulin-like Receptor (KIR) genotypes in Follicular Lymphoma patients: Results of a pilot study

AimsThe Natural Killer Cell Immunoglobulin-like Receptor (KIR) genotype profiling in Follicular Lymphoma has not been reported before in the literature. Materials and methodsDNA extracted from 20 Follicular Lymphoma patients and 62 healthy controls was analyzed for KIR genotyping using a polymerase chain reaction/sequence specific primers technique (PCR/SSP) for the presence of 16 KIR gene and pseudogene loci. ResultsThe AA, AB, and BB genotype frequencies were, respectively, 20%, 60% and 20% with an A:B ratio of 1:1. KIR 2DL4, KIR 3DL2, KIR 3DL3, and KIR 3DP1*003 were presented in all individuals. No significant difference between patients and controls was detected. ConclusionKIR genotyping profile does not seem to be associated with Follicular Lymphoma. The results presented in this pilot research represent the first international report about this important clinical entity.

Low producer MBL genotypes are associated with susceptibility to systemic lupus erythematosus in Odisha, India

Variants of MBL gene have been associated with autoimmune disorders. The aim of this study was to explore whether common polymorphisms in MBL gene are associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort from eastern India. A total of 108 female SLE patients and 105 age, sex, and ethnically matched healthy controls were enrolled in the study. MBL2 codon and promoter polymorphisms were genotyped by AS-PCR and dARMS PCR, respectively. Plasma level of MBL was quantified by ELISA. Higher frequency of BB genotype and minor allele (B) was observed in patients of SLE compared to healthy controls (BB genotype: P = 0.0002; OR = 5.75, 95% CI = 2.09-15.76, B allele: P < 0.0001; OR = 2.78, 95% CI = 1.66-4.64). MBL codon 54, H-550L, Y-221X polymorphisms and combined MBL genotypes contributed to plasma MBL levels. Prevalence of MBL low producer genotype (LXA/LYB, LYB/LYB and LXB/LXB) was significantly higher in SLE patients compared to healthy control. (P = 0.005; OR = 3.09, 95% CI = 1.38-6.91). On analysis of clinical manifestations, MBL low producer genotype was significantly associated with autoimmune haemolytic anaemia (P = 0.006; OR = 13.06). Results of the present study indicate MBL2 variants as possible risk factors for development of SLE and clinical manifestation in eastern India.

BsmI, TaqI, ApaI, and FokI polymorphisms in the vitamin D receptor gene and periodontitis: a meta-analysis of 15 studies including 1338 cases and 1302 controls

A meta-analysis was conducted in order to investigate the potential association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to aggressive and chronic periodontal disease. A database search yielded a total of 15 studies involving 1338 cases and 1302 controls. Four polymorphisms were included in the meta-analysis: VDR TaqI (rs731236), VDR BsmI (rs1544410), VDR FokI (rs2228570), and VDR ApaI (rs7975232). Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the distribution of alleles and genotypes between cases and controls. The combined results based on all studies showed that (1) chronic periodontitis cases had a significantly lower frequency of bb genotype of BsmI [OR=0.63, 95% CI=0.42, 0.94; p=0.02] in Asians; (2) chronic periodontitis cases had a significantly higher frequency of AA genotype of ApaI (OR=2.20, 95% CI=1.39, 3.48; p<0.001) in Asians; (3) chronic periodontitis cases had a weak significantly higher frequency of TT genotype of TaqI (OR=1.86, 95% CI=1.002, 3.46; p=0.049) in Asians. After Bonferroni's correction, we found that in Asians chronic periodontitis cases still had a significantly higher frequency of AA genotype of ApaI. No significant difference was found in any genotype of FokI. No association was found for all the VDR gene polymorphisms examined as far as the aggressive form of the disease is concerned. Future studies need to focus on the possible biological consequences and mechanisms of the VDR genetic variants. The current findings confirm that VDR gene is a candidate gene for periodontitis.

Association between SNP rs10569304 on the second expressed region of hole gene and the congenital heart disease

The correlation of single nucleotide polymorphism (SNP) rs10569304 on the second expressed region of hole gene and congenital heart disease (CHD) of human being, and the effect of hole gene on CHD were investigated. 179 patients with CHD as CHD group and 183 healthy people as control group were selected in the case-control study. DNA was abstracted from the peripheral blood by phenol-chloroform method. Primer was designed for the flanking sequence of SNP rs10569304 on the second expressed region of hole gene. The genotype was identified by PCR degenerative acrylamide electrophoresis with amplification products. Then the three amplification products received sequencing. By chi-square test, the genotype frequency and allele frequency in CHD group and control group were analyzed. There was insertion-deletion (GCC/-) of SNP rs10569304 which corresponded to alleles of A and B in Southern Chinese people. The genotype frequency and allele frequency in control group and CHD group were met the Hardy-Weinberg equilibrium. By chi-square test, in control group and CHD group, the genotype frequency of AA (insertion homozygous), AB (insertion-deletion heterozygous) and BB (deletion homozygous) was 21.31%, 54.09%, 24.59% and 16.75%, 46.36%, 36.87%, respectively. The distributional difference of genotype frequency had statistical significance (chi2=6.51, P<0.05); The allele frequency of A and B was 48.36% and 51.64% in control group, 39.94% and 60.06% in CHD group, respectively. The distributional difference of allele frequency had statistical significance (chi2=5.20, P<0.05). Meanwhile, by contrast with the control group, the BB genotype frequency and B allele frequency in CHD group was higher, but the AA and AB frequency was lower. There was higher risk to suffer from CHD involving B allele. BB genotype had 1.907-fold increased risk of developing CHD according to AA genotype (P<0.05). It is concluded that there is insertion-deletion (GCC/-) of SNP rs10569304 in the Southern Chinese people, and the people whose hole gene involving BB genotype have higher risk to suffering from CHD.

BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: A meta-analysis

Context Vitamin D receptor (VDR) gene polymorphisms have been strongly associated with bone mineral density in some studies. However, in a recent meta-analysis, no relationship of the VDR BsmI or TaqI polymorphism and fracture risk was found in the meta-analysis of published data. Objective and design Our meta-analysis studied whether a relationship exists between BsmI, TaqI, ApaI and FokI polymorphisms in the VDR gene and risk of fracture. Data sources Relevant studies were identified from the following electronic databases: MEDLINE, EMBASE and Current Contents before January 2010. Data synthesis This meta-analysis included 17 studies with a total of 21 eligible comparisons, which included 2112 fracture cases and 4521 controls. All of these studies reported on Caucasians. The combined results based on all studies showed that fracture cases had a significantly lower frequency of bb genotype of BsmI [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.76, 0.98]. When stratifying by fracture type, we found that (1) hip fracture cases had a significantly lower frequency of bb genotype of BsmI (OR = 0.82, 95% CI = 0.70, 0.97); (2) hip fracture cases had a significantly lower frequency of Tt genotype of TaqI (OR = 0.65, 95% CI = 0.43, 0.97); (3) hip fracture cases had a significantly higher frequency of tt genotype of TaqI (OR = 1.74, 95% CI = 1.05, 2.91); (4) vertebral fracture cases had a significantly higher frequency of Aa genotype of ApaI (OR = 1.63, 95% CI = 1.03, 2.59). No significant difference was found in any genotype of FokI. Conclusion Our meta-analysis suggests that there is a modest but statistically significant association between the BsmI bb genotypes and fracture.

Polymorphism Identification of Pit1 Gene in Indonesian Buffaloes (Bubalus bubalis) and Holstein-Friesian Cows

Pit-1 gene has been identified as the pituitary specific transcription factor that regulates the expression of the growth hormone (GH) and prolactin (PRL) genes in the anterior pituitary. The use of polymorphic markers in breeding programmes could make selection more accurate and efficient. A total of 320 Indonesian buffaloes from four populations and 45 FH cows from nine populations were genotyped for polymorphism of Pit1|Hinf1 gene by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods. The gene polymorphism was detected only in FH cattle. The frequency of AA, AB, and BB genotype was 2%, 44%, and 53% respectively. The frequency of A allel was 25% and B allel was 75%, but no polymorphism was detected in 320 Indonesia buffaloes.

Vitamin D receptor gene polymorphisms: no association with low bone mineral density in adolescent idiopathic scoliosis girls

To investigate the association of vitamin D receptor (VDR) gene polymorphisms with low bone mineral density (BMD) in adolescent idiopathic scoliosis (AIS) girls. Blood samples were obtained from 146 AIS girls and 146 healthy girls. Anthropometric parameters of AIS group including age, body height, weight and Cobb angle were all recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect and analyze VDR gene distributions of AIS group and control group. BMD of the lumbar spine (L(1)-L(4)) and proximal femur were measured using dual energy x-ray absorptiometry in AIS group. The frequency of Bb genotype was significantly higher in patients than that in controls (P < 0.05). There was no distinction among the lumbar spine and proximal femur BMD of each genotype in AIS group (P > 0.05). VDR gene polymorphisms have no association with the low spine lumbar and proximal femur BMD in AIS girls.

P-Selectin Glycoprotein Ligand-1 VNTR Polymorphisms in Systemic Sclerosis.

Systemic sclerosis (SSc) is a systemic connective tissue disease characterized by excessive fibrosis, vascular injury, autoimmunity and inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) expressed on leukocytes and microparticles derived from myeloid cells is major counter-receptor for P-selectin. P-selectin and PSGL-1 crosslinking mediates interaction among leukocytes, platelets and endothelial cells during thrombosis, inflammation, and angiogenesis.It has been postulated that the recently defined “variable number tandem repeats” (VNTR) polymorphisms of the mucin-like region of PSGL-1 might effect the adhesion function by changing the interaction between P-selectin and PSGL-1. We aimed to investigate the distribution of PSGL-1 VNTR polymorphisms in SSc and to compare with the healthy controls in order to study the role of these polymorphisms in the pathogenesis of SSc and its complications. One hundred and fourteen SSc patients (102 women, 12 men) who fulfilled 1980 ACR preliminary criteria and 203 unrelated healthy controls (98 women, 105 men) were studied. Demographic and clinical characteristics of the patients were recorded by using a standart form. The study was approved by the local ethical committee and subjects signed informed consent documents. PSGL-1 polymorphisms were determined with PCR method (1). 4 genotypes were identified after genotyping according to bands in gel electrophoresis (AA, AB, BB, AC). Cumulative frequencies of A, B and C alleles in SSc were 77.2%, 21.5% and 1.3%, respectively and 82.4%, 15.4% and 2.2% in the control group. The AA, AB, BB and AC genotype frequencies were 59.6%, 32.5%, 5.3% and 2.6% in SSc and 70%, 21.2%, 4.9% and 3.9% in control group. 37 of 114 SSc patients were carrying the AB genotype (32.5% vs 21.2%, OR=1.79, 95% CI 1.07–3.0, p=0.027). B allele carriers were 37.7% in SSc and 26.1% in control group (OR=1.71, 95% CI 1.04–2.80, p=0.031). When two major disease subsets were considered, AB genotype was found to be more frequent in patients with limited cutaneous involvement (lSSc) (34.8% vs 21.2%, OR=1.99, 95% CI 1.084–3.65, p=0.025). However, the frequency of AB genotype in diffuse systemic sclerosis (dSSc) was similar to that of control group (p=0.75). Similarly, B allele carriers were more frequent in lSSc (40.9% vs 26.1%, OR=1.96, 95% CI 1.1–3.5, p=0.022). When the clinical and laboratory characteristics of patients were taken into consideration, AB genotype was significantly less frequent in anti-Scl70 positive patients compared to anti-Scl70 negative patients (21.8% vs. 42.9%, OR=0.37, 95% CI 0.16–0.85, p=0.018). Likewise, B allele carriers were less frequent in anti-Scl70 positive patients (29.4% vs. 49.1%, OR=0.43, 95% CI 0.19–0.96, p=0.038). The AB genotype was increased in patients with arthritis compared to patients with no arthritis (77.8% vs. 28.3%, OR=8.87, 95% CI 1.73–45.35, p=0.002). PSGL-1 VNTR polymorphisms were distributed significantly different in SSc and healthy controls when clinical subsets of SSc were analysed seperately. The AB genotype and B allele were significantly more frequent in lSSc. This finding was also supported by the low frequency of AB genotype and B allele in anti-Scl70 positive patients, which is more common in dSSc. PSGL-1 VNTR polymorphisms might play a role in the pathogenesis of lSSc by modifying leukocyte, platelet and endothelial cell interactions. Further research is needed to confirm the relationship with AB genotype and arthritis in SSc patients.

Vitamin D receptor gene polymorphisms are not associated with alopecia areata

It has been demonstrated that the vitamin D receptor (VDR) is strongly expressed in key structures of hair follicles, and a lack of VDR leads to alopecia. We investigated whether there was any association between VDR gene polymorphisms (BsmI, ApaI, and TaqI) and alopecia areata (AA). Thirty-two patients with AA and 27 healthy control subjects were genotyped using polymerase chain reaction and restriction fragment length polymorphism analysis. In the patient group, the B and b allele frequencies were 53.1% and 46.9%, A and a allele frequencies were 70.3% and 29.7%, and T and t allele frequencies were 62.5% and 37.5%, respectively. In the control group, the corresponding values were 51.9% and 48.1%, 63.0% and 37.0%, and 77.8% and 22.2%, respectively. In the patient group, the BB, Bb, and bb genotype frequencies were 25.0%, 56.2%, and 18.8%, AA, Aa, and aa genotype frequencies were 43.8%, 53.1%, and 3.1%, and TT, Tt, and tt genotype frequencies were 37.5%, 50.0%, and 12.5%, respectively. In the control group, the corresponding values were 11.1%, 81.5%, and 7.4%, 29.6%, 66.7%, and 3.7%, and 63.0%, 29.6%, and 7.4%, respectively. None of the allele or genotype frequencies showed statistically significant differences between the patient and control groups. These findings suggest that there is no relationship between VDR gene polymorphisms and AA.

Vitamin D receptor gene polymorphisms in female adolescent idiopathic scoliosis patients

To investigate the association of vitamin D receptor (VDR) gene polymorphisms with abnormal growth pattern and low bone mass in adolescent idiopathic scoliosis (AIS) patients. Peripheral blood samples were obtained from 164 female patients with AIS, aged 14.4 +/- 2 (9 - 20), and 122 age-matched healthy girls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the VDR gene distributions. The frequency of Bb genotype was significantly higher in the AIS patients than in the controls (P < 0.01). The frequency of B alleles of the AIS patients was significantly higher than that of the controls (P < 0.01). In AIS patients, the expression rate of Aa genotype of the AIS patients with the body mass index (BMI) > or = 18 kg/m(2) was significantly higher than those with the BMI < 18 kg/m(2) (P < 0.05), and the expression rate of Bb genotype of the AIS patients with the BMI < 18 kg/m(2) and arm span < 160 cm was significantly higher than that of the AIS patients with the BMI > or = 18 kg/m(2) and arm span > or = 160 cm (P < 0.05). The BsmI site polymorphism of vitamin D receptor gene may be associated with abnormal growth pattern and low bone mass in girls with AIS.

Polymorphism of ZuBeCa3 microsatellite and its association with mammary tumor in dogs

A study was conducted to explore the genetic polymorphism at ZuBeCa3 microsatellite and to estimate the association between microsatellite polymorphism and mammary cancer in dogs. Three genotypes namely AA, AB and BB were observed both in dogs affected by mammary cancer and in non-affected dogs. In the affected group, the frequency of genotype and allele was 0.63 for AA, 0.25 for AB and 0.12 for BB genotype, and 0.76 for A and 0.24 for B allele. In the nonaffected group, the frequency of AA, AB and BB genotype was 0.39, 0.38 and 0.23 and the frequency of A and B allele was 0.58 and 0.42, respectively. Histopathological observation classified the cancer-affected animals into three groups namely, malignant solid mammary carcinoma, malignant papillary adenocarcinoma and benign papillary adenoma in which the frequency of A allele was relatively more predominant in benign tumor group, which is more than 80%. Statistical tests showed significant differences (P < 0.01) of allelic distribution between tumor-affected and non-affected group, which reveals the effect of polymorphism on occurrences of mammary cancer in dogs. Besides, chi(2) test also reflected the significant effect of genotypes on occurrences of three groups of mammary cancer in dogs.

Association between cutaneous melanoma, Breslow thickness and vitamin D receptor BsmI polymorphism

Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. All cases and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Non‐relation of Parathyroid Hormone Gene Polymorphisms to Secondary Hyperparathyroidism in Chinese Hemodialysis Patients

Objective: To investigate the relationship between parathyroid hormone (PTH) gene polymorphisms and secondary hyperparathyroidism in Chinese hemodialysis (HD) patients. Materials and Methods: 210 patients in one HD unit were enrolled as the study group and 203 age‐matched health subjects were enrolled as controls. PTH genotypes were determined by polymerase chain reaction and restricted fragment length polymorphisms (RFLPs) of BstBI and DraII. B and b or D and d were indicated by the presence or absence, respectively, of BstBI and DraII at restriction sites on the PTH gene. Serum iPTH levels and serum total calcium (Sca), phosphate (Sp), bone‐specific alkaline phosphatase (bAlk), and aluminum (Al) levels across different genotypes were compared. Results: When polymorphisms at the BstBI the restriction site were investigated, the patients' BB, Bb, and bb genotype frequencies were 62%, 37%, and 1%, respectively. At the DraII restriction site, the patients' DD, Dd, and dd genotype frequencies were 78%, 17%, and 5%, respectively. No significant differences were found across the three genotypes, BB, Bb, and bb, in serum Sca, Sp, bAlk, Al and iPTH levels. DraII cleavage PTH gene polymorphisms displayed a similar pattern. Patients with BBDD haplotype were not found to have significantly higher serum iPTH levels than those with other haplotypes. Conclusion: Our study appears to indicate that PTH gene polymorphisms do not influence serum iPTH levels in Chinese HD patients.

The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients

Background: Both in vitro and in vivo studies have shown that calcitriol, the active form of vitamin D, is involved in hematopoiesis. We hypothesized that the vitamin D receptor (VDR) genotype, which may differentiate response to endogenous or exogenous active vitamin D, has a role in the management of anemia in hemodialysis (HD) patients. Methods: The VDR BsmI gene polymorphism was determined in 91 HD patients and 85 healthy controls. In addition to well-known factors responsible for both anemia and inadequate response to erythropoietin (EPO), we examined the contribution of the VDR genotype to hematocrit (Hct), hemoglobin (Hb) level, total weekly dose of EPO, and EPO-Hb ratio as an index of patient EPO need. Results: Genotype distributions for the VDR gene were under the Hardy-Weinberg equilibrium and similar in patients and controls (genotypes BB, Bb, and bb: 22.0%, 38.5%, and 39.5% in patients versus 24.7%, 48.2%, and 27.1% in controls). There were statistically significant differences in Hct, Hb level, EPO dose, and EPO-Hb ratio in patients with the three BsmI genotypes, whereas the other parameters were the same. Comparison of patients with an Hb level less than versus greater than 11 g/dL showed that the former patients had lower albumin levels (P = 0.001), higher C-reactive protein levels (P = 0.014), and a greater frequency of BB genotype (P < 0.001). Similarly, comparison of patients with an EPO-Hb ratio in the highest quartile versus those in the lowest quartile showed that the former patients had lower albumin and transferrin levels (P = 0.013 for both) and greater frequencies of BB genotype (P = 0.016). In logistic regression analysis, both BB genotype and low serum albumin level were found to be the only independent predictors for an Hb level less than 11 g/dL (P < 0.001 and P = 0.046, respectively). Both parameters also predicted being in the highest quartile of EPO-Hb ratio (P = 0.004 for both). Conclusion: The VDR BsmI gene polymorphism may predict both Hb level and EPO need in HD patients. However, because the underlying mechanisms have not been clarified in the present study, further research on this issue is needed. © 2002 by the National Kidney Foundation, Inc.

Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis

Vitamin D receptor (VDR) polymorphisms have been strongly associated with bone mineral density (BMD) in some studies but not in others. We used a meta-analytic approach to assess quantitatively the association between VDR and BMD and to examine the influence of specific study characteristics (e.g., skeletal site, mean age of subjects, menopausal status) on the reported results. Sixteen papers published in peer-reviewed journals through July 1996 were included. We calculated the mean difference, percent difference, and effect size (mean difference divided by standard deviation), comparing BMD between homozygous genotypes. At the hip, BMD in the BB genotype was lower than in the bb genotype (mean difference, -0.02 g/cm2; percent difference, -2.4% and effect size -0.18; p = 0.032). At the spine, the mean difference was -0.03 g/cm2; percent difference, -2.5%; and effect size, -0.19; p = 0.062. At the distal radius, the VDR effect was estimated as the mean difference, -0.01 g/cm2; percent difference, -1.7%; and effect size, -0.16; p = 0.078. The spine measurements exhibited the greatest between- and within-study variability. The difference in hip BMD between genotypes was larger (i.e., a more negative number) among the younger women and seemed to decrease with increasing age. However, statistical evidence for this trend was weak (p = 0.06). Data from the spine and the radius showed no evidence of a comparable interaction of the VDR effect with age. When we omitted data from the first report of an association between VDR polymorphisms and BMD, our analyses gave similar results, although the overall effect estimates were smaller. In the combined data from 29 study groups, the BB genotype frequency was 17.2, 4.9, and 2.3% in studies of whites, blacks, and Asians, respectively. VDR polymorphisms represent one genetic factor affecting BMD, but further research into the mechanisms, clinical significance, and its relation between other genetic and environmental factors is needed.