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PubMed2004

Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density.

UNLABELLED: In this study, we evaluated the effect of polymorphisms of the CYP1A1 gene, linked to hormone-related cancers, on estrogen metabolism and BMD. We found that variants carrying the A allele (CA and AA) for the C4887A polymorphism have a significantly higher degree of estrogen catabolism and lower femoral BMD. INTRODUCTION: Polymorphisms of the CYP1A1 gene, one of the key enzymes that metabolize estrogen, have been linked with hormone-related cancers. We investigated the impact of these polymorphisms on estrogen metabolism and BMD, which is another hormone-dependent health issue. MATERIALS AND METHODS: One hundred seventy postmenopausal women (mean age, 63.5 +/- 0.6 years) participated in the study, but analysis was limited to 156 white women. Genotyping was performed by restriction fragment length polymorphism analysis, urinary estrogen metabolites by enzyme immunoassay, serum estradiol by ultrasensitive radioimmunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and BMD by DXA. Differences in the levels of urinary metabolites and BMD among the different variants were analyzed by analysis of covariance, whereas differences in free estradiol index, urinary N-telopeptide of type 1 collagen (NTx), and bone size were compared by one-way ANOVA. RESULTS: We found that subjects carrying the A allele (CA or AA) for the C4887A polymorphism of the CYP1A1 gene have significantly lower free estradiol index (0.323 +/- 0.08 versus 0.506 +/- 0.04; p = 0.04; pmol/nmol) and higher levels of total urinary estrogen metabolites (ng/mg Cr) than CC subjects (27.92 +/- 2.03 versus 21.15 +/- 1.04; p = 0.03), suggestive of an accelerated estrogen catabolism in these (CA + AA) individuals. They also had significantly lower BMD (g/cm2) in all regions of the femur than subjects with the CC genotype, (total hip: 0.809 +/- 0.02 versus 0.865 +/- 0.01; neck: 0.671 +/- 0.02 versus 0.722 +/- 0.01; trochanter: 0.614 +/- 0.02 versus 0.656 +/- 0.01; and intertrochanter: 0.969 +/- 0.03 versus 1.039 +/- 0.01; all p < 0.05). No significant effect of this gene polymorphism was detected on lumbar spine BMD. Urinary NTx, a marker for bone resorption, was also significantly higher in the CA + AA compared with the CC variants (186.09 +/- 16.15 versus 124.00 +/- 11.87 nmol of bone collagen equivalent/mmol of creatinine; p = 0.003). Genotype frequencies for this polymorphism showed CC as the most common genotype (127/156), followed by CA (28/156), whereas AA was rare (1/156). CONCLUSION: Women with the A allele seem to have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites and lower free estradiol index. This is associated with increased bone resorption and lower femoral BMD in those with the A allele. Our data, therefore, suggest that, through its effect on the rate of estrogen catabolism, the C4887A polymorphism of the CYP1A1 gene may represent a possible genetic risk factor for osteoporosis.

Absorptiometry, Photon↗
PubMed2002

Klotho gene polymorphisms associated with bone density of aged postmenopausal women.

Because mice deficient in klotho gene expression exhibit multiple aging phenotypes including osteopenia, we explored the possibility that the klotho gene may contribute to age-related bone loss in humans by examining the association between klotho gene polymorphisms and bone density in two genetically distinct racial populations: the white and the Japanese. Screening of single-nucleotide polymorphisms (SNPs) in the human klotho gene identified 11 polymorphisms, and three of them were common in both populations. Associations of the common SNPs with bone density were investigated in populations of 1187 white women and of 215 Japanese postmenopausal women. In the white population, one in the promoter region (G-395A, p = 0.001) and one in exon 4 (C1818T, p = 0.010) and their haplotypes (p < 0.0001) were significantly associated with bone density in aged postmenopausal women (> or = 65 years), but not in premenopausal or younger postmenopausal women. These associations were also seen in Japanese postmenopausal women. An electrophoretic mobility shift analysis revealed that the G-A substitution in the promoter region affected DNA-protein interaction in cultured human kidney 293 cells. These results indicate that the klotho gene may be involved in the pathophysiology of bone loss with aging in humans.

Aged↗
PubMed2002

Association of interleukin-1 receptor antagonist gene polymorphism with IgA nephropathy.

It is evident that cytokines play an important role in the pathogenesis as well as disease progression of IgA nephropathy (IgAN). Several gene polymorphisms of the pertinent cytokines have an influence on the level of cytokine production. Interleukin-1 receptor antagonist (IL-1ra) gene polymorphism has been found to affect disease susceptibility and activity in several inflammatory diseases. In the present study, we analyzed polymorphism of the variable number tandem repeat (VNTR) of IL-1ra in patients diagnosed as having IgAN (n = 106) and normal controls (n = 74). The allele frequency of IL-1ra polymorphism in IgAN patients was not statistically different from that of the control group. There was no significant difference in the carriage rate of the two-repeat allele (IL1RN*2) between IgAN patients and the control group (8.5 vs. 6.8%). The carriage rate of IL1RN*2 was significantly higher in IgAN patients with severe proteinuria (>or=1.6 g/day) or increased serum creatinine level (>or=2.0 mg/dl; p < 0.05). Furthermore, the carriage rate of IL1RN*2 was significantly higher in patients with severe mesangial cell proliferation (p < 0.01). Our results suggest that IL-1ra polymorphisms are not associated with the development of IgAN in Japanese patients but the presence of IL1RN*2 may be associated with increased disease activity.

Alleles↗
PubMed2004

Cholecystokinin- and cholecystokinin-B-receptor gene polymorphisms in panic disorder.

Panic disorder like other neuropsychiatric disorders is believed to be caused by multiple psychosocial and biological factors. Several lines of evidence point to a role for the peptide neurotransmitter cholecystokinin in the pathogenesis of panic disorder. We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls. The length of the polymorphic CT repeat alleles varies between 146 bp and 180 bp. We first analysed the results by a permutation test which provided evidence for heterogeneity between patients and controls (p=0.002). We then analysed the data as a di-allelic polymorphism with a short (146-162bp) and a long (164-180bp) allele and as a tetra-allelic polymorphism with 4 alleles (146-154bp, 156-162bp, 164-170bp, 172-180bp). In the di-allelic analysis as well as in the tetra-allelic analysis there was an excess of the longer allele (p = 0.001) or the two longer alleles (p = 0.041) respectively in patients with panic disorder. No difference between groups was observed for the -36C > T polymorphism. Our findings are consistent with the notion that genetic variation in the CCK neurotransmitter system contributes to the pathogenesis of panic disorder.

Adult↗
PubMed2001

[The relationship between angiotensin converting enzyme gene polymorphism and risk factors for cerebral infarct].

OBJECTIVE: To explore the relationship between angiotensin converting enzyme (ACE) gene polymorphism and risk factors of cerebral infarct (CI) in Chinese Han nationality. METHODS: One hundred and sixty-five cases with cerebral infarct, 101 cases of essential hypertension patients with 106 normal persons in Chinese Han serving as controls were detected using polymorase chain reaction (PCR) and genetic methods. ACE contents in serum were measured by colorimetric method. Risk factors of cerebral infarct were assessed by standard questionnaire, physical examination and blood tests. RESULTS: ACE DD genotype appeared more common in patients of cerebral infarct when comparing with essential hypertension groups (0.43 versus 0.31, chi 2 = 4.03, P < 0.05) and normal controls (0.43 versus 0.17, chi 2 = 19.86, P < 0.01). D:I allele frequency appeared to be 0.66:0.34 in cerebral infarct patients and 0.41:0.59 in controls (chi 2 = 32.85, P < 0.01). In basal ganglia infarct and thalamus infarct groups, ACE DD genotype and allele ratio distribution were remarkably different to that in normal subjects (chi 2 = 18.30, 12.41, P < 0.01). The mean levels of serum in cerebral and hypertension were higher than in normal controls (F = 2,240.06, P < 0.01), and serum ACE activity in ACE DD genotype was significantly higher than that in ACE DI and II genotype in cerebral group (F = 8.83, P < 0.01). CONCLUSIONS: The ACE gene deletion polymorphism might serve as an independent risk factor for cerebral infarct in Chinese Han nationality while circulation ACE activity might be related to gene deletion polymorphism.

Adult↗
PubMed2003

Association between pepsinogen C gene polymorphism and genetic predisposition to gastric cancer.

AIM: To identify a molecular marker for gastric cancer, and to investigate the relationship between the polymorphism of pepsinogen C (PGC) gene and the genetic predisposition to gastric cancer. METHODS: A total of 289 cases were involved in this study. 115 cases came from Shenyang area, a low risk area of gastric cancer, including 42 unrelated controls and 73 patients with gastric cancer. 174 cases came from Zhuanghe area, a high-risk area of gastric cancer, including 113 unrelated controls, and 61 cases from gastric cancer kindred families. The polymorphism of PGC gene was detected by polymerase chain reaction (PCR) and the relation between the genetic polymorphism of PGC and gastric cancer was examined. RESULTS: Four alleles, 31 0bp (allele 1), 400 bp (allele 2), 450 bp (allele 3), and 480 bp (allele 4) were detected by PCR. The frequency of allele 1 was higher in patients with gastric cancer than that in controls. Genotypes containing homogenous allele 1 were significantly more frequent in patients with gastric cancer than that in controls (0.33, 0.14, chi(2)=3.86, P<0.05). There was no significant difference between the control group of Zhuanghe and the group of gastric cancer kindred. But the frequency of allele 1 was higher in control group of Zhuanghe area than that in control group of Shenyang area and genotypes containing homogenous allele 1 were significantly more frequent in the control group of Zhuanghe area than those in control group of Shenyang area (0.33, 0.14, chi(2)=4.32, P<0.05). In the group of gastric cancer kindred the frequency of allele 1 was significantly higher than that in control group of Shenyang area (0.5164, 0.3571, chi(2)=4.47, P<0.05). Genotypes containing homogenous allele 1 were significantly more frequent in the group of gastric cancer kindred than those in control group of Shenyang area (0.36, 0.14, chi(2)=4.91, P<0.05). CONCLUSION: These results suggest that there is some relation between pepsinogen C gene polymorphism and gastric cancer, and the person with homogenous allele 1 predisposes to gastric cancer than those with other genotypes. Pepsinogen C gene polymorphism may be used as a genetic marker for a genetic predisposition to gastric cancer. The distribution of pepsinogen C gene polymorphism in Zhuanghe, a high-risk area of gastric cancer, is different from that in Shenyang, a low risk area of gastric cancer.

Alleles↗
PubMed2005

Serotonin transporter gene polymorphism and migraine in the Korean population.

OBJECTIVE: To evaluate the association between a serotonin (5-HT) transporter gene polymorphism and migraines in Koreans. BACKGROUND: The 5-HT metabolism is believed to play an important part in the pathophysiology of migraines, and a polymorphism of the serotonin transporter (5-HTT) promoter region might influence 5-HTT expression and serotonin uptake. METHODS: This study compared 52 patients with migraine and 170 healthy control subjects in order to determine the association between a polymorphism of the 5-HTT gene-linked polymorphic region (5-HTTLPR) and migraine. Using PCR techniques, the products of the 484-base pair (bp) fragments were denoted as being short alleles (s) and those of 528 bp as being long (l). RESULTS: The genotype distribution of the healthy controls was s/s (56.5%), s/l (38.2%), and l/l (5.3%) and that of the patients with migraine was 65.4%, 30.8%, and 3.8%, respectively. No significant differences were noted in the genotype and allele frequencies of 5-HTTLPR between the patients with migraine and the control subjects. CONCLUSIONS: A 5-HTTLPR polymorphism does not appear to be involved in the genetic predisposition to migraines.

Adolescent↗
PubMed1999

[Genetic analysis of candidate gene polymorphisms in elderly hypertension].

Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging.

Aged↗
PubMed2005

CTLA-4 gene polymorphisms in Chinese patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by chronic inflammation of the colon and rectum as a result of an exaggerated T-cell response. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a T cell-restricted surface molecule induced with TCR or CD28 activation. There is evidence for genetic involvement of CTLA-4 in several autoimmune diseases, with the focus on the possible role of genetic variation of the CTLA-4 locus. The aim of this study was to investigate CTLA-4 gene polymorphisms in patients with UC in a Chinese population with Han nationality. METHODS: The C-318T polymorphism in the promoter region and A+49G polymorphism in exon 1 of the CTLA-4 gene were studied by a polymerase chain reaction-sequence-specific primer method. We studied 82 unrelated patients with UC and 204 healthy controls in a Chinese population with Han nationality. RESULTS: The frequency of the haplotype 2,3 (-318C+49G/-318T+49A) was 26% in patients with UC and 41% in healthy controls (Fisher exact test P = 0.0147, odds ratio = 0.4918, 95% confidence interval: 0.2784 - 0.8688), but this significance disappeared when Bonferoni correction was applied. No other significant differences in the distribution of allele and genotype frequencies were observed between C-318T and A+49G gene polymorphisms and UC in the Chinese Han population. CONCLUSION: The C-318T and A+49G polymorphisms of the CTLA-4 gene were not associated with UC in Chinese Han patients.

Adolescent↗
PubMed2001

Nitric oxide synthase gene polymorphisms in Alzheimer's disease and dementia with Lewy bodies.

Evidence suggests that vascular and inflammatory components may be important in the aetiology of dementia and genetic risk factors affecting these processes may therefore influence disease development. Recently, polymorphisms in the endothelial constitutive nitric oxide synthase 3 (NOS3) and also the inducible nitric oxide synthase gene (NOS2A) have been suggested to lead to increased risk of Alzheimer's disease (AD) or dementia with Lewy bodies. We have studied the relationship of both these NOS gene polymorphisms to development of AD and dementia with Lewy bodies and find no evidence for association with either condition. We conclude that NOS gene polymorphisms do not alter disease risk in the majority of late-onset dementia cases.

Aged↗
PubMed2002

Recurrent aphthous stomatitis and gene polymorphisms for the inflammatory markers TNF-alpha, TNF-beta and the vitamin D receptor: no association detected.

OBJECTIVE: To investigate the possibility that minor recurrent aphthous stomatitis (MiRAS) is associated with the inheritance of specific gene polymorphisms for markers associated with macrophage driven inflammation, i.e. tumor necrosis factor-alpha (TNF-alpha), TNF-beta or the vitamin D receptor (VDR). SETTING: MiRAS is a common, painful, ulcerative condition of the mouth. Its etiology is unknown although mononuclear inflammatory cells are thought to play an important role. There is no clear genetic mode of inheritance, however, many patients report a positive family history and disease concordance is significantly higher in monozygotic than dizygotic twins, suggesting a polygenic mode of inheritance. METHODS: Ninety-five MiRAS patients and an ethnically matched control population were genotyped for TNFA-308, TNFB Ncol and VDR (intron 8 and exon 9) polymorphisms. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. RESULTS: No significant association was identified between inheritance of specific alleles or genotypes of the TNFA-308, TNFB Ncol and VDR (intron 8 and exon 9) polymorphisms and susceptibility to MiRAS. CONCLUSIONS: Inheritance of specific gene polymorphisms for TNF-alpha, TNF-beta or VDR does not appear to be a significant factor in determining susceptibility to MiRAS.

Adult↗
PubMed2005

Cytochrome P450 gene polymorphisms and risk of low birth weight.

This study investigated the association between polymorphisms in cytochrome P450 genes (CYP1A1MspI, CYP1A1HincII, and CYP2E1) and low birth weight. Between July 1999 and June 2002, we conducted a study using infant-parents triads in Anqing, China. The analyses included the families of 248 normal birth weight, full-term infants, and 248 low-birth-weight infants. Genotyping was performed for the polymorphisms of cytochrome P450 genes using standard techniques. We used log-linear modeling to analyze the association of CYP1A1 and CYP2E1 gene polymorphisms with the risk of low birth weight. In the analysis of children's genotypes, the relative risk was 1.92 (95% confidence interval: 1.05, 3.52, p=0.034) for CYP1A1MspI C/C6235 compared with CYP1A1 MspI T/T6235. In the analysis of mothers' genotypes, an association was also seen for maternal CYP1A1MspI C/C6235 compared with CYP1A1MspI T/T6235 (relative risk: 1.68, 95% confidence interval: 1.06, 2.68, p=0.029). We did not observe a joint effect between mother's and children's genotypes. Analysis of control triads suggests Mendelian transmissions of the variant alleles of CYP1A1MspI, CYP1A1HincII, and CYP2E1. In conclusion, both infant and maternal CYP1A1MspI C/C6235 genotypes were associated with increased risk of low birth weight in our study population. This suggests a possible role for human cytochrome P450 variability in the etiology of low birth weight.

Alleles↗
PubMed1991

HLA-DR and the 5' insulin gene polymorphism in insulin-dependent diabetes.

While the human leukocyte antigen (HLA) region provides the major susceptibility for insulin-dependent (type I) diabetes mellitus (IDDM), other (non-HLA) genes must also play a role. Population studies have shown an increased frequency of small insertions (class I alleles) 5' to the insulin gene in individuals with IDDM, suggesting that this region may account for part, if not all, of the non-HLA genetic predisposition. However, no data are available as to whether the relation of the insulin gene polymorphism is to a DR-defined subset of IDDM or with all of IDDM. To test the hypothesis that specific combinations of HLA and insulin gene polymorphism alleles may interact in providing susceptibility for IDDM, HLA-DR and 5' insulin gene insertion size have been determined in 300 individuals with IDDM. The frequency of class 1 insulin gene alleles in the entire sample is 0.79 and the frequency of class 3 alleles (large inserts) is 0.20. The frequencies of class 1 alleles were equal across all DR classes: 0.79 in the DR3/X IDDM subjects, 0.80 in the DR4/X, 0.79 in the DR3/4, and 0.78 in those with DRX/X. Additionally, the frequencies of class 1/1 homozygotes and 1/3 heterozygotes were similar between HLA-DR types. These results suggest that the HLA region and the region 5' to the insulin gene provide independent and nonsynergistic genetic risks for IDDM.

Diabetes Mellitus, Type 1↗
PubMed1998

Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals.

Adult↗
PubMed2003

Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression.

Recent studies showed that a polymorphism (T to C nucleotide substitution) in the 3' flanking region of the human CLOCK gene is associated with diurnal preferences of human healthy subjects, with higher "eveningness" in subjects carrying at least one copy of the C allele. We investigated the possible role of CLOCK gene polymorphism in the regulation of diurnal mood fluctuations during a major depressive episode. Sample (n = 101) was collected, in the context of previously reported trials, among patients affected by bipolar disorder type I, depressive episode without psychotic features, free of psychotropic medications. Perceived mood levels were assessed three times a day with self-administered visual analogue scales. Genotype groups showed no significant difference in diurnal mood fluctuations. When stratifying the sample by including only patients with an adequate period of observation (duration of illness higher than 5 years, n = 69), we post-hoc observed a significantly higher recurrence rate in homozygotes for the C variant, which was almost double than that of the other genotype groups. This preliminary observation leads to hypothesize a role for the CLOCK gene polymorphism in the regulation of long-term illness recurrence in bipolar disorder. Given the post-hoc nature of the finding, replication in independent samples is necessary to confirm it.

Bipolar Disorder↗
PubMed2000

Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis.

OBJECTIVE: Vulvar vestibulitis is a chronic inflammatory syndrome of unknown cause and pathogenesis. We examined the relation between vulvar vestibulitis and polymorphisms in the gene coding for the interleukin 1 receptor antagonist, a naturally occurring down-regulator of proinflammatory immune responses. STUDY DESIGN: Cells from the lower genital tract of 68 women with vulvar vestibulitis, 343 women with no history of vulvodynia, and 40 women with human papillomavirus cervical infection were tested by polymerase chain reaction for the different alleles of the gene encoding for interleukin 1 receptor antagonist. The presence of human papillomavirus in the specimens was determined by polymerase chain reaction with the use of degenerate consensus primers to the conserved L1 gene. RESULTS: Allele 2 of the gene encoding the interleukin 1 receptor antagonist was present in homozygous form in 52.9% of women with vulvar vestibulitis. In marked contrast only 8. 5% of the control women and 2.5% of women with human papillomavirus were homozygous for this allele (P </=.0001). Among the women with vulvar vestibulitis, 57.5% of those without human papillomavirus, as well as 52.2% of those with human papillomavirus, were homozygous for allele 2 of the gene encoding interleukin 1 receptor antagonist. CONCLUSION: The unique distribution of interleukin 1 receptor antagonist alleles among women with vulvar vestibulitis suggests that polymorphism in this gene may be a factor influencing susceptibility to this syndrome, severity of symptoms, or both.

Alleles↗
PubMed2004

Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis.

BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis.

Adult↗
PubMed2006

TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases.

Recent studies have revealed elevated expression of transforming growth factor beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and those undergoing ulcer repair. As production of TGF-beta1 is genetically regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene are involved in susceptibility to and clinical characteristics of Helicobacter pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200 with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction and RFLP analysis. H. pylori infection and CagA/VacA antibody status were determined by Western blot in patients and controls. H. pylori infection (odds ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non-steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were identified as independent risks factors for duodenal ulcer (DU), whereas the TGFB1+869(*)C/C genotype was associated with reduced risk of developing the disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1 T+869C gene polymorphism is involved in the susceptibility to DU and provide further evidence that host genetic factors play a key role in the pathogenesis of H. pylori-related diseases.

Aged↗