Sp1 Binding Site Polymorphism Research Articles

COLIA1 + 1245 G > T Sp1 Binding Site Polymorphism is Not Associated with ACL Injury Risks Among Indian Athletes.

Type I collagen polypeptides contribute significantly to the structural composition of ligament tissue matrix. Since anterior cruciate ligament (ACL) tears account for roughly 50% of all knee injuries in sports, the objective of the study was to investigate association of Sp1-transcription factor binding site polymorphism COLIA1 Sp1 + 1245 G > T with ACL injury risk among Indian athletes. A total of 166 athletes (90 with ACL tears and 76 as control) were recruited and were genotyped for COLIA1 Sp1 + 1245 G > T polymorphism using allele-specific PCR (AS-PCR) method. Both the groups were matched for nature of sports, training regimen, and other demographic characteristics. We observed no significant difference between ACL cases and control group in GT or TT genotype frequency distribution (p = 0.967) and T-allele frequency distribution (p = 0.861) for COLIA1 Sp1 + 1245 G > T polymorphism. Also, the three models of inheritance of minor allele failed to show any statistical significance in the present study. COLIA1 Sp1 + 1245 G > T polymorphism has been studied in relation to many connective tissue pathologies. This is probably the first study to investigate the association of collagen protein genes with ACL injury risk on Indian athletes. Further studies with more SNPs in genes encoding fibril-forming collagen and large sample sizes are necessary to fully understand the genetic link to ACL injuries among athletes.

Sp1 Binding Site Polymorphism at COL1A1 Gene and Its Relation to Bone Mineral Density for Osteoporosis Risk Factor Among the Sikkimese Men and Women of Northeast India

Single nucleotide polymorphism in the first intron of Collagen type I alpha 1 (COL1A1) gene which is the binding site of specificity protein 1 (Sp1) transcription factor associated with low bone mineral density and osteoporosis. To evaluate such genetic factors among the Sikkimese population, a total of 150 cases (75 men and 75 women) with primary osteopenia and osteoporosis and 150 healthy controls (75 men and 75 women) of age range between 35 and 65years were enrolled in this study. The COL1A1 genotypes [SS, Ss and ss] were assessed by restriction enzyme [MscI] digestion of DNA after amplification by polymerase chain reaction. There, only 2.7% women and 1.3% men cases had restriction site with heterozygous genotype (Ss) and no homozygous genotype (ss) were detected. There was no statistically significant association between low bone mass and genotypes on analysis (χ2=1.014, P=0.314; RR=1.510) that, theSp1binding site polymorphism at the COLIA1gene is very rare and has no contribution in the development low bone mineral density.

Sp1 binding site polymorphism of a collagen gene (rs 1800012) in women aged 45 and over and its association with bone density.

Sp1 polymorphism of type I collagen genes is accompanied with bone collagen disorders and severe clinical phenotypes such as osteogenesis imperfecta. The aim of this study was to study the association between COLIA1 Sp1 polymorphism and bone density rate. In this descriptive, analytical study conducted in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenol-chloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. The genotype distribution of Sp1 polymorphism for the SS, Ss, and ss genotypes was 57.1%, 31.4%, and 11.4%, respectively, in the control group and 9.2%, 75.4%, and 15.4%, respectively, in the patients. Statistically, Sp1 polymorphism in patients had a significant deviation (P = 0.00 1, χ2 = 34.25) and there was no Hardy-Weinberg equilibrium. In the control group, there was no significant deviation for Sp1 polymorphism (P = 0.226, χ2 = 2.97). Sp1 polymorphism was significantly associated with bone density. Women with the SS genotype had the highest bone density. Sp1 gene polymorphism is associated with bone density rate in women aged 45 and over, and is more commonly observed in homozygosity. Determining this genotype's polymorphism is valuable to identify the women at risk of developing osteoporosis.

Is Sp1 binding site polymorphism within COL1A1 gene associated with tennis elbow?

Tennis elbow defines a condition of pain and tenderness over the lateral epicondyle of the humerus. The exact aetiology of the injury is not yet fully understood. The major constituent of tendons is type 1 collagen which is encoded by COL1A1 gene. The aim of the study was to determine whether Sp1 binding site polymorphism (SNP rs1800012; 1546G/T) within the intronic region of COL1A1 gene is associated with tennis elbow. One hundred and three tennis elbow patients and one hundred and three healthy subjects without any history of previous ligament or tendon injuries were recruited for this genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism by using PCR–RFLP method. There were no observed statistical differences in the genotype (p=0.17) or allele (p=0.11) distributions between the groups. G allele frequency in patients and controls was 82.5% and 76.21%, and T allele frequency was 17.5% and 23.79% respectively. This study has shown that there is no association between this polymorphism and tennis elbow within the population studied.

Association of collagen type I alpha 1 gene polymorphism with inguinal hernia

A positive family history is an important risk factor for inguinal hernia development, suggesting a genetic trait for hernia disease. However, gene mutations responsible for abdominal wall hernia formation in humans have not yet been studied. We aimed to evaluate whether the functional Sp1 binding site polymorphism within intron 1 of the collagen type I, alpha 1 (COL1A1) gene was associated specifically with inguinal hernia disease. 85 participants with surgically diagnosed inguinal hernia disease, and 82 physically active controls without any history of connective tissue disease and hernia were recruited for this case-control genetic association study. Polymerase chain reaction and restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to detect these polymorphisms. Significantly, more patients gave a positive family history for an inguinal hernia compared to healthy controls (OR 3.646, 95 % CI 1.375-9.670, P = 0.006). COL1A1 Sp1 SNP (rs 1800012) was identified. Results demostrated statistically significant deviation from HWE for cases (P = 0.007), but not for the controls (P = 0.276). Our results revealed an increased frequency of COL1A1 Sp1 Ss genotype in inguinal hernia patients (OR 3.593, 95 % CI 1.867-6.915, P = 0.000). This results suggest that polymorphism of the COL1A1 Sp1 binding site is associated with an increased risk for developing inguinal hernias. So, rs 1800012 locus is a potential candidate region for susceptibility in molecular mechanism of inguinal hernia pathophysiology.

An SP1-binding site polymorphism in the COLIAI gene and osteoporosis in Egyptian patients with thalassemia major

β-Thalassemia major is an inherited blood disorder, which mainly affects the Mediterranean region. Osteoporosis represents an important cause of morbidity in β-thalassemia major and its pathogenesis has not been completely clarified. Genetic factors play an important role in the pathogenesis of osteoporosis and several candidate gene polymorphisms have been implicated in the regulation of this process. A G→T polymorphism in the regulatory region of the collagen type I alpha 1 (COLIAI) gene at a recognition site for transcription factor Sp1 has been strongly associated with osteoporosis. The aim of the present study was to examine the distribution of COLIAI polymorphism and its relationship with bone mineral density (BMD) at the lumbar spine and femur in patients and controls. In this study, the G→T polymorphism was detected in 31 Egyptian β-thalassemia major patients and 20 healthy controls and its possible association with BMD was investigated. Alleles S and s were detected by the presence of a G or T nucleotide, respectively, in a regulatory site of the COLIAI gene using polymerase chain reaction (PCR). A total of 80.6% of the β-thalassemia patients were homozygous for G/G (SS) and 19.4% were heterozygotes for G/T (Ss) polymorphism. There was no ss genotype in our patients. In the control group, 70 and 30% had SS and Ss genotypes, respectively. There was no significant difference between Z-score of patients with SS and Ss at head of femur (P = 1) or at lumbar spine (P = 0.48). Conclusion Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying the thalassemic patients at risk of developing osteoporosis.

Sp1 polymorphism in collagen I α1 gene is associated with osteoporosis in lumbar spine of Mexican women

The Sp1 binding site polymorphism in collagen type I alpha 1 gene (COLIA1) has been associated with osteoporosis (OP) and bone mineral density (BMD). The aim of this study was to explore the association of this polymorphism with OP and BMD in the Mexican population by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) procedure. Allelic and genotypic frequencies from the Sp1 polymorphism were determined in 100 women with OP, 100 women without OP and 500 subjects from general Mexican population (GMP). Distribution of Sp1 polymorphism was in Hardy-Weinberg equilibrium. In spite of population structure due to racial mix in Mexican population, associations with OP were demonstrated. The frequency of "s" allele was significantly higher in women with OP (35%) than in women without OP (11%; P < 0.00001). Interestingly, "ss" genotype, was exclusive of women with OP and was associated with low BMD (0.588 ± 0.077 g/cm(2)) in contrast to "SS" genotype (0.733 ± 0.039 g/cm(2); P = 0.0001). This work confirms the association of Sp1 polymorphism with low BMD and OP in Mexican population and make sure to use Sp1 as a genetic marker for OP in our population.

Does COLIA1 SP1-binding site polymorphism predispose women to pelvic organ prolapse?

COLIA1 polymorphism is associated with increased risk for stress urinary incontinence. We hypothesize that a similar association exists with pelvic organ prolapse (POP). Patients with advanced prolapse and healthy controls were evaluated by interview, validated questionnaires, and pelvic examination. DNA was extracted from peripheral blood, and polymerase chain reaction was performed to determine the presence or absence of the polymorphism. Power calculation indicated the need for 36 patients in each arm. The prevalence of the polymorphic heterozygous genotype (GT) in the study and control groups was 33.3% and 19.4%, respectively, leading to an odds ratio of 1.75. This difference, however, did not reach statistical significance (p = 0.27). The COLIA1 polymorphism was not significantly associated with increased risk for POP.

Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant

Background:Anterior cruciate ligament (ACL) ruptures are considered the most severe injury sustained in sports. Although various intrinsic and extrinsic risk factors have been identified, the exact aetiology of the injury...

COL1A1 Sp1-binding site polymorphism as a risk factor for genital prolapse

The objective of this study was to verify the possible association between the Sp1-binding site polymorphism and genital prolapse. A case-control study was conducted in 107 patients with stages III and IV genital prolapse. The control group included 209 women with stages 0 and I. The polymorphism of type I collagen Sp1-binding site was identified by amplification of the first intron of the COL1A1 gene. We did not find differences in the prevalence of the GT and TT genotypes between the groups (p = 0.34), even when we grouped patients with at least one polymorphic allele (GT and TT) and compared them with patients without the polymorphic allele (GG; p = 0.17) The presence of at least one vaginal delivery, family history for prolapse, and macrosomatic fetus were independent risk factors for prolapse. In conclusion, the COL1A1 Sp1-binding site was not significantly associated with genital prolapse among our study subjects.

Investigation of the Sp1-binding site polymorphism within the COL1A1 gene in participants with Achilles tendon injuries and controls

Sequence variants within the type V collagen (COL5A1) and tenascin C (TNC) genes have to date been shown to be associated with chronic Achilles tendinopathies and/or spontaneous Achilles tendon ruptures. Type V collagen and tenascin C are quantitatively minor components of tendon, while type I collagen is the major structural component. There is increased expression of the COL1A1 gene, which encodes for the alpha1 chain of type I collagen, in the painful Achilles tendon. A functional Sp1-binding site polymorphism (SNP rs1800012; IVS1+1023G>T) within this gene has been shown to be associated with several connective tissue disorders. The aim of this study was to determine whether the Sp1-binding site polymorphism within the COL1A1 gene is associated with chronic Achilles tendinopathies and/or spontaneous Achilles tendon ruptures. Achilles tendinopathy (n=85), Achilles rupture (n=41) and asymptomatic control (n=125) participants were genotyped for the COL1A1 Sp1-binding site polymorphism. There were no observed statistical differences in the genotype (p=0.602) or allele (p=0.694) distributions between the groups. In conclusion, this study has shown that there is no association between the Sp1-binding site polymorphism within the first intron of COL1A1 and Achilles tendinopathy or Achilles tendon rupture within the population studied.

Effects of hormone replacement therapy on bone mineral density in Turkish patients with or without COL1A1 Sp1 binding site polymorphism

To evaluate the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in patients with or without COL1A1 Sp1 binding site polymorphism. Non-smoking otherwise healthy postmenopausal women (n=111), who had not received any kind of HRT for at least 3 years (between 2002 and 2005) at the onset of menopause, were included. All patients received 0.625 mg conjugated estrogen/2.5 mg medroxyprogesterone for 18 months. BMD by dual X-ray absorptiometry was measured at the lumbar spine and the femur neck initially and after 18th months of treatment. COL1A1 Sp1 binding site polymorphism was studied using the PCR-RFLP method. After having the results of COL1A1 Sp1 binding site polymorphism, 79 (71.2%) patients were SS, 30(27.0%) were Ss and two (1.8%) were homozygous for ss. The mean age, weight and length of menopausal period were similar between the SS and Ss patients. The Ss heterozygotes had lower BMD values both at the lumbar spine and at the femur neck compared with the SS patients. This difference was also reflected in post treatment measurements. The increase in BMD scores was higher in the SS homozygotes than in the Ss patients. Our preliminary data supports the fact that HRT had a lower increase in BMD scores following 18 months of treatment in COL1A1 s allele individuals compared with normal SS individuals. Therefore our study may provide evidence that the Sp1 polymorphism may ameliorate the effects of HRT on BMD, suggesting some additional regimens may be used to support bone strength and to decrease osteoporotic fractures.

Collagen type 1 (COL1A1) Sp1 binding site polymorphism is associated with osteoporotic fractures but not with bone density in post-menopausal women from the Canary Islands: a preliminary study

An association between the polymorphism for transcription factor Sp1 in the gene COL1A1 and low bone density (BMD) and osteoporotic fractures has been described but not confirmed for all races and ages. The aim of this preliminary work was to ascertain whether this association is present in women from the Canary Islands. Polymerase chain reaction RFLP was used to determine COL1A1 polymorphism Sp1 in 199 consecutive outpatient post-menopausal Caucasian women from the Canary Islands, aged 50-70 years. BMD was measured at lumbar spine and hip by DXA and at third lumbar vertebrae by QCT. Prevalent vertebral fractures were recorded on standard lateral X-ray film. Non-vertebral osteoporotic fractures were registered by medical record and self-reported history. Biochemical markers (serum osteocalcin, tartrate-resistant acid phosphatase), blood calcium and phosphate were also assessed. Distribution genotypes were 113 (50.8%) GG homozygotes, 73 (36.7%) Ss heterozygotes and 7 (3.5%) TT homozygotes. All patients with osteoporotic fractures carried the GG allele more frequently than TT homozygotic women. The odds ratio was 3.01 (95% CI 1.6-5.7) for prevalent vertebral fractures (n=62) and 2.33 (95% CI 1.2-4.4) for all osteoporotic fractures (n=65) for the T-carrying allele vs TT homozygotic women. There was no difference in BMD measured by DXA or QCT, nor in bone markers, blood calcium or phosphate. This preliminary study confirmed that the presence of at least one copy of the T allele is associated with osteoporotic fractures, but not with low BMD, in women from the Canary Islands.

An α-1 chain of type 1 collagen Sp1-binding site polymorphism in women suffering from stress urinary incontinence

An α-1 chain of type 1 collagen Sp1-binding site polymorphism in women suffering from stress urinary incontinence

A rapid one-tube PCR method for simultaneously differentiating homozygotes and heterozygotes of the Sp1 binding site polymorphism in collagen type Iα1

Rapid detection of single-base changes is fundamental to molecular medicine. PCR amplification of specific alleles (PASA) has previously been used as a rapid method of genotyping single-nucleotide changes, but one reaction is required for each allele. This paper describes a Bidirectional PASA (Bi-PASA) method, which was developed to distinguish between homozygotes and heterozygotes in one PCR reaction. The method is tested using the Sp1 polymorphism in Collagen type Ialpha1. The results demonstrate that Bi-PASA is a simple and rapid method for detecting the zygosity of the polymorphism in a single PCR reaction.

Myocardial infarction is associated with Sp1 binding site polymorphism of collagen type 1A1 gene

Objective — Human atherosclerotic lesions contain collagen type 1, which plays a pivotal role in atherosclerotic plaque stability. In contrast, the normal coronary arteries do not express this type of collagen. Data have shown that the collagen type 1A1 (COL1A1) gene Sp1 binding site (-1245 G/T) polymorphism is associated with disturbed collagen protein production.Methods — In our study, COL1A1 gene Sp1 polymorphism was investigated in 136 patients with myocardial infarction (MI) 5 months after the acute phase, and 212 age-matched control subjects in association with any cardiovascular risk factors (such as serum adiponectin levels, hyperinsulinaemic status, hyperlipaemia).Results — The “SS” genotype of the COL1A1 gene was found to occur significantly more frequently in patients surviving a MI, as compared to the control group and the “Ss” and “ss” genotype frequencies (the presence of the s allele) were lower in our patients, than in control group. However, the occurrence of cardiovascular risk factors was significantly higher among the “s” allelic carriers as compared to patients carrying the “S” allele of the COL1A1 gene.Conclusion — Our results raise the possibility that COL1A1 gene Sp1 polymorphism might have an impact on the development of MI.

An α-1 chain of type I collagen Sp1-binding site polymorphism in women suffering from stress urinary incontinence

We examined the possible influence of G-->T substitution in transcription factor Sp1-binding site in the gene encoding alpha-1 chain of type I collagen on the risk of stress urinary incontinence. The study group consisted of 50 women reporting symptoms of stress urinary incontinence. Fifty control subjects were treated for benign gynecological conditions other then stress urinary incontinence. DNA was obtained from peripheral blood leukocytes. The fragment of the first intron of the gene encoding the alpha-1 chain of type I collagen containing the Sp1-binding site was amplified by polymerase chain reaction. The analysis of restriction fragment length polymorphism was performed. We found association between the GT and TT genotype and stress urinary incontinence (P = .019). The odds ratio for developing stress urinary incontinence is 4.98 (95% confidence interval 1.97 to 12.56) in subjects presenting the GT genotype and 2.23 (95% confidence interval 0.69 to 7.25) for the TT genotype. The G-T polymorphism at the Sp1 binding site of the gene encoding alpha-1 chain of type 1 collagen is associated with increased risk of stress urinary incontinence in women.

Effects of Hormone Replacement Therapy (HRT) and Alendronate on Bone Mineral Density (BMD) in Patients With Col 1 A1 Sp 1 Binding Site Polymorphism a Prospective Randomized Study

Osteoporosis is a common disease with genetic component. It has been shown that polymorphic Sp1 site is associated with osteoporosis. We tried to evaluate the effects of HRT and alendronate on BMD in patients with Col1A1 Sp1 binding site polymorphism and its possible role in bone collagen turnover.

Association of otosclerosis with Sp1 binding site polymorphism in COL1A1 gene: evidence for a shared genetic etiology with osteoporosis.

There is an association between otosclerosis and osteoporosis. Both osteoporosis and otosclerosis are common bone diseases to which relatively large portions of the population are genetically predisposed. Recently, a strong association has been described between osteoporosis and an Sp1 binding site of putative functional significance in the first intron of the COL1A1 gene. We applied polymerase chain reaction-based restriction enzyme analysis to determine the polymorphic distribution of the Sp1 site in 100 patients with otosclerosis and 108 control subjects. This study showed a significant association between otosclerosis and the COL1A1 first intron Sp1 site. The allelic frequency of the Sp1 site is very similar between otosclerosis and osteoporosis. Some cases of otosclerosis and osteoporosis could share a functionally significant polymorphism in the Sp1 transcription factor binding site in the first intron of the COL1A1 gene.

Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women.

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.