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PubMed2004

Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland.

Functional genetic polymorphisms of DNA repair genes are good candidates for cancer susceptibility markers. We studied two genes coding for proteins removing small DNA adducts by direct repair (MGMT), or mispaired DNA bases by base excision repair (TDG). The non-silent polymorphisms of MGMT (84:Phe, 143:Val, 178:Arg) and TDG (199:Ser, 367:Met), and the functional MGMT enhancer polymorphism, did not show any statistically significant association with lung cancer risk in our case-control analysis, but due to the relatively small number of individuals, strong conclusions on cancer risk association or lack thereof cannot be made. Sequencing of the TDG cDNA has not revealed any novel polymorphism, but did find an alternatively spliced mRNA missing exon 2. Our search for polymorphisms within the promoter-enhancer region of MGMT revealed three novel sequence variants. The functional significance of the previously published MGMT enhancer polymorphism (1099C->T) was assessed. The less frequent sequence variant of the enhancer was associated with a modest (16-64%), but statistically significant, increase of MGMT promoter-enhancer activity in the studied cell lines. This work points to the importance of studying the expression-regulating elements of genes, as they may contain functional polymorphisms with the potential for modulating risk of various diseases, including cancer.

Adult↗

PubMed2002

Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo Study.

Vitamin D receptor (VDR) polymorphism influences susceptibility to type 1 diabetes, but the association with type 2 diabetes is not clear. We investigated the association between VDR polymorphism and type 2 diabetes and metabolic syndrome in a community-based study of unrelated older adults without known diabetes. Oral glucose tolerance test (75 g), plasma glucose and insulin measurement, homeostasis model assessment (HOMA), and VDR genotyping were performed. The distributions of genotype frequencies of ApaI, BsmI, and TaqI polymorphism did not differ between persons with and without diabetes, but the frequency of aa genotype of ApaI polymorphism was marginally higher in persons with type 2 diabetes (P =.058). Fasting plasma glucose (P <.05) and prevalence of glucose intolerance (P <.05) were significantly higher in nondiabetic persons with aa genotype compared with those with AA genotype. The bb genotype of BsmI polymorphism was associated with insulin resistance as assessed by HOMA after adjustment for age, sex, body mass index (BMI), and calcium and vitamin D use in persons without diabetes (P <.05). Our research suggests that ApaI polymorphism may be associated with glucose intolerance independent of defective insulin secretion and BsmI polymorphism with insulin resistance in a nondiabetic Caucasian population.

Aged↗

PubMed2000

Neither IL-1beta, IL-1 receptor antagonist, nor TNF-alpha polymorphisms are associated with susceptibility to COPD.

The cytokines that contribute to airway inflammation, including interleukin-1beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha), might have key roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin-1 receptor antagonist (IL-1RN), the physiological antagonist of IL-1beta, is also known to play a crucial role in several chronic inflammatory diseases. In this study, we investigated the association of the polymorphisms of IL-1beta, IL-1RN and TNFalpha with susceptibility to COPD. To elucidate the genotype of the IL-1beta polymorphisms at position -511 base and at the amino acid residue 105, the IL-1RN polymorphism in intron 2, and TNFalpha polymorphism at position -308, polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) were performed on blood samples from both patients with COPD (n = 53) and control subjects (n = 65). There were no differences on the allele and genotype frequency of IL-1beta, IL-1RN, and TNFalpha between the two groups. We could not find a significant link between the polymorphism of TNFalpha, which was previously reported to be associated with chronic bronchitis, and COPD. Furthermore, no association between genetic polymorphisms of IL-1beta and IL-1RN and individual susceptibility to COPD was found.

Aged↗

PubMed2006

The Leu7Pro polymorphism of neuropeptide Y is associated with younger age of onset of type 2 diabetes mellitus and increased risk for nephropathy in subjects with diabetic retinopathy.

Several studies have shown genetic predisposition for diabetic complications. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY has been shown to be a risk factor for diabetic retinopathy in type 1 diabetes. In the current study we examined the contribution of this polymorphism on the progression of retinopathy in Caucasian type 1 and type 2 diabetes patients. Patients with type 2 diabetes and the Leu7Pro polymorphism developed retinopathy at younger age because of markedly earlier disease onset of diabetes (RC- 6.8, 95% CI-12.2 - [- 1.5]), but no association of the Leu7Pro polymorphism with the current severity of retinopathy was detected. A strong association of the polymorphism with proteinuria in type 2 diabetes patients with retinopathy could be detected (OR 3.1, 95% CI 1.1-8.8); 31% of subjects having both retinopathy and proteinuria had the polymorphism compared to only 13% of retinopathy patents without concomitant proteinuria (p = 0.032). Plasma concentrations of NPY were increased in subjects with proteinuria (79.2+/-28.4 and 64.7+/-26.2 pmol/l, p = 0.001). These results suggest that the Leu7Pro polymorphism could be used to predict earlier onset of type 2 diabetes and retinopathy, and increased risk for diabetic nephropathy.

Adult↗

PubMed2006

RAS and MTHFR gene polymorphisms in a healthy exercise-trained population: association with the MTHFR (TT) genotype and a lower hemoglobin level.

The aim of this study was to determine the frequencies of ACE (I/D), AGT (M235T), AT1R (A1166C) and MTHFR (C677T) polymorphisms in a well-defined (in regards to health and nutritional status and lifestyle) population of young, healthy, exercise-trained subjects (no. 100) from the Campania region of Southern Italy. We also investigated whether there was any correlation between these polymorphisms and biochemical, hematological and hemostatic parameters in this "low-risk" population. Gene polymorphisms were analyzed with the polymerase chain reaction and restriction enzyme analysis. Allele frequencies of the genotypes examined were in Hardy-Weinberg equilibrium and agree with those reported in the Italian population. No associations were found between ACE, AGT, AT1R gene polymorphisms and anthropometric, clinical and laboratory parameters. However, the MTHFR (C677T) polymorphism was significantly associated with lower hemoglobin plasma levels in TT vs. CC + CT females (p < 0.016). This report is the first to describe the frequencies of RAS and MTHFR gene polymorphisms in young, exercise-trained volunteers from Campania and to identify an association between the MTHFR gene polymorphisms and lower hemoglobin plasma levels in young healthy females.

Adult↗

PubMed2006

The K121Q polymorphism of the plasma cell glycoprotein-1 gene is not associated with diabetes mellitus type 2 in German Caucasians.

The K121Q polymorphism of the human plasma cell membrane glycoprotein 1 (PC-1) gene is known to be associated with diabetes mellitus type 2 in some populations studied, with contradictory results. The purpose of the present study was to examine a possible association between the presence of diabetes and the PC-1 K121Q polymorphism in a German Caucasian population. Associations between the polymorphism and various metabolic and anthropometric parameters were also examined. The presence of the K121Q variant was investigated using polymerase chain reaction restriction fragment-length polymorphism in 402 subjects with diabetes (231 men, 171 women, age 63+/-11 yrs, body mass index 28.7+/-5.1 kg/m2) and in 432 age- and sex-matched controls (247 men, 185 women, age 64+/-7 yrs, BMI 26.5+/-3.7 kg/m2). Ninety-seven subjects were carriers of the K121Q polymorphism in the control and 110 in the diabetic group (allelic frequency 11.9% and 14.7%, respectively, P=0.25). The polymorphism had no significant influence on the presence of atherosclerotic disease, body mass index, and blood pressure, both, in diabetics and in non-diabetic controls. Our data suggest that the K121Q polymorphism of the PC-1 gene is not associated with diabetes, obesity, hypertension or atherosclerosis in a German Caucasian population.

Adult↗

PubMed2000

A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.

BACKGROUND: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. OBJECTIVE: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. METHODS: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3' untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. RESULTS: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated (P =.000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. CONCLUSION: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype.

Asthma↗

PubMed2001

Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B.

BACKGROUND: Increasing evidence indicates that total serum IgE levels are largely determined by genetic factors, and we recently established that the -109C/T promoter polymorphism at FCER1B is a genetic factor that affects total serum IgE levels. The gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) is another candidate factor in high IgE responsiveness, because B7-CD28/CTLA4 interaction can promote the differentiation and development of the T(H)2 lymphocyte subset. OBJECTIVE: We intended to determine whether CTLA4 is associated with increased levels of total serum IgE or with the development of asthma or atopy. METHODS: We performed a case-control study involving 339 patients with asthma and 305 healthy control subjects, of whom 226 of the patients with asthma and 219 of the healthy control subjects had previously been genotyped for the -109C/T promoter polymorphism at FCER1B. In the current study, we genotyped 2 polymorphisms in the CTLA4 gene, one involving the promoter (-318C/T) and the other involving exon 1 (+49A/G), in addition to the FCER1B promoter polymorphism. RESULTS: Patients with asthma who were homozygous for the -318C allele at the CTLA4 promoter region had higher levels of total serum IgE than patients with asthma carrying the -318T allele (P =.00470). The analysis of -318C/T (at CTLA4) and -109C/T (at FCER1B) promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in patients with asthma (P =.000014). In contrast, no correlation between total serum IgE levels and -318C/T or +49A/G genotypes was detected in 305 healthy control subjects. There was no evidence indicating an association between a putative allele for asthma or atopy and alleles at any of the CTLA4 polymorphic loci. CONCLUSION: Our findings suggest that promoter polymorphisms of both CTLA4 and FCER1B are genetic factors that influence total serum IgE levels in patients with asthma. This supports the theory that variance in total serum IgE levels in patients with asthma is determined by mutations in multiple genes, each of which has a relatively small effect on the phenotype.

Abatacept↗

PubMed2001

The -590C/T and -34C/T interleukin-4 promoter polymorphisms are not associated with atopic eczema in childhood.

Susceptibility to the development of asthma and other atopic diseases is known to have a genetic component. To date, several studies have linked chromosome 5q31 to asthma and atopy in human beings. This region harbors a cluster of cytokine and growth factor genes, IL-4 presenting as a prime atopy candidate gene, inasmuch as it plays a pivotal role in the atopy pathway. Our approach was to identify polymorphisms within the promoter regions of IL-4 and test their association with atopic eczema. Polymorphisms were typed in a cohort of 76 small nuclear families and 25 triads with childhood atopic eczema. The genotypes were used to test for linkage in the presence of association with atopic eczema. A new polymorphism, -34C/T, was identified and studied with a known polymorphism, -590C/T. On its own, each polymorphism showed no association with atopic eczema. The 2 polymorphisms were used to generate haplotypes, and a significant result was found for the -590C/-34C haplotype. However, after Bonferroni correction for multiple testing, the association became nonsignificant. Neither polymorphism predisposes to early-onset atopic eczema by itself, but suggestive linkage was found for the -590C/-34C haplotype in this study.

Child↗

PubMed2003

Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization.

OBJECTIVE: Polymorphic variants of the human progesterone receptor gene have been described, but their potential influence on in vitro fertilization outcome have not been studied. STUDY DESIGN: DNA was available from 317 women (cases) who had >or=2 embryo transfers without a clinical pregnancy and from 288 women (control subjects) who became pregnant after 1 in vitro fertilization attempt. With protocols that were specific for H770H (C/T genotype) and +331G/A polymorphism, amplification of polymorphism fragments, digestion with restriction enzymes, and gel visualization were performed. RESULTS: Allele frequencies for the 2 variants were 15.5% for H770H T and 4.1% for +331A in cases and 17.9% and 3.6% in control subjects, respectively. Both polymorphisms were rare among non-white subjects. Possession of a H770H T allele was associated with a decreased risk for implantation failure, which was nonsignificant overall but significant in women aged <35 years (adjusted relative risk, 0.52 [95% CI, 0.28, 0.97]). Possession of a +331A allele was associated with an increased risk of implantation failure, which was nonsignificant overall but significant in women who weighed <135 pounds (adjusted relative risk, 3.85 [95% CI, 1.20, 12.30]). The +331G/A polymorphism tended to increase the risk for implantation failure in women with an H770H C/C genotype, but not in women with a C/T or TT genotype (P=.09). Among white women who were H770H C/C, there was a significant trend (P=.03) in the proportion of +331G/A carriers as the number of implantation failures increased, from 8.6% of women with 0 failed attempts to 40% among women with >or=5 failed attempts. CONCLUSION: Although human progesterone receptor polymorphisms do not clearly affect the risk for implantation failure in most women who undergo in vitro fertilization, the likelihood that a woman carries the +331G/A human progesterone receptor polymorphism increases with the number of failed attempts at implantation.

Adult↗

PubMed2004

Interlocus nonrandom association of polymorphisms in Drosophila chemoreceptor genes.

Some forms of multilocus selection with epistasis, such as truncation selection, can effectively reduce the mutation load [Kondrashov, A. S. (1988) Nature 336, 435-440]. Many quantitative characters, including complex genetic diseases, are likely to be subject to these types of selection. However, direct measurement of selection in natural populations is difficult and the effect of epistasis on within-species variations remains unclear. Epistatic interaction in the fitness effect can generate linkage disequilibrium (LD). Therefore, we may detect the action of natural selection from its amount and pattern. Here, we report a large number of interlocus nonrandom associations between polymorphisms in 98 Drosophila chemoreceptor genes. LD was examined in two fly samples collected at the same location, but in different seasons. The amount of LD was much larger in the spring sample than in the autumn one. The between-sample difference was much more striking for the replacement polymorphisms than for the silent polymorphisms. This difference between the replacement and silent polymorphisms could not be attributed to differences in the mean marker distances. We also found a significant excess of associations between one frequent and one less common allele for the replacement polymorphisms, but not for the silent polymorphisms. It is unlikely that a simple seasonal bottleneck could explain all these differences in the scale of LD between the samples and between the replacement and silent polymorphisms. Natural selection is suggested to play a significant role in shaping the pattern of LD observed in this study.

Alleles↗

PubMed2004

Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects.

The presynaptic alpha2C adrenergic receptors (AR) act to inhibit norepinephrine release in cardiac and other presynaptic nerves. We have recently shown that a genetic variant in the alpha2CAR coding region (Del322-325), which renders the receptor partially uncoupled from Gi, is a risk factor for heart failure. However, variability of heart failure phenotypes and a dominance of Del322-325 in those of African descent led us to hypothesize that other regions of this gene have functional polymorphisms. In a multiethnic population, we found 20 polymorphisms within 4,625 bp of contiguous sequence of this intronless gene encompassing the promoter, 5' UTR, coding, and 3' UTR. These polymorphisms occur in 24 distinct haplotypes with complex organizations, including multiple 5'-upstream polymorphisms in regions known to direct expression, a 3' UTR substitution polymorphism within an insertion/deletion sequence, and the radical coding polymorphism that deletes four amino acids. Relatively low linkage disequilibrium between many polymorphisms, few cosmopolitan haplotypes, prevalent ethnic-specific haplotypes, and substantial genetic divergence among haplotypes was noted. The dysfunctional Del322-325 allele was partitioned into multiple haplotypes, with frequencies of 48% to 2%. The functional implications of the haplotypes were ascertained by whole-gene transfections of human neuronal cells, where haplotype was significantly related (P < 0.001) to expression levels of receptor transcript and protein. Expression varied by as much as approximately 50% by haplotype, and such studies enabled haplotype clustering by phenotypic, rather than genotypic, similarities. Thus, depending on phenotype, expression-specific haplotypes may amplify, attenuate, or dominate the cardiomyopathic effect attributed to the alpha2CDel322-325 marker.

Haplotypes↗

PubMed1983

Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man.

DNA probes containing the switch region (S) associated with the human immunoglobulin heavy chain mu gene were used to investigate polymorphisms in the germ-line human DNA. Six polymorphisms, detected by a single restriction enzyme (Sst I) are described. Linkage studies in 29 families show that five of the six polymorphisms, although relatively unassociated in random individuals, segregate in complete linkage one to the other and to Gm allotypes (markers on the heavy chain of IgG), while the sixth segregates independently. Altogether, when one considers the DNA markers at the five closely linked loci and the IgG1 and IgG3 heavy chain allotypes, 33 different haplotypes have been described; of these, 28 are detected by the DNA polymorphism alone. Study of 158-187 random haplotypes showed strong linkage disequilibrium only between one DNA polymorphism (Sst A) and Gm. Of the polymorphic Sst I loci, one, Sst E [associated with 2.2- to 2.7-kilobase (kb) fragments], is included in the mu chain S region (S mu); another, Sst A (6.8-7.4 kb), must be very close to the gamma 1-gamma 3 chain gene cluster. Based on studies of an IgE human myeloma, a third polymorphism, Sst C (4.8-5.5 kb), should map 3' of the active epsilon chain gene. An Sst I restriction enzyme map of phage clones carrying the two alpha chain genes indicates that Sst A and Sst C loci probably overlap with the alpha 1 and alpha 2 S regions, respectively. Both deletion/duplications and point mutations were detected.

Chromosome Deletion↗

PubMed1983

Analysis of HLA class I genes with restriction endonuclease fragments: implications for polymorphism of the human major histocompatibility complex.

Cellular DNA from HLA-typed individuals was digested with the restriction endonucleases HindIII, EcoRV, and EcoRI. The separated restriction endonuclease fragments were hybridized with a HLA class I cDNA probe by using the Southern transfer technique. Digestion of cellular DNA with HindIII generated 22 restriction endonuclease fragments, 11 of which showed polymorphism for presence or absence in a population sample. With EcoRV, 13 fragments were identified; 6 showed polymorphism. EcoRI generated 11 fragments, of which 1 was polymorphic. Of these 18 polymorphic fragments generated by the three restriction endonucleases, each of 5 was found to be positively associated with one allele of the HLA-A or -B allelic series (HLA-Aw24, -B8, -B15, -Bw35, and -B40). One fragment was positively associated with two HLA-A series alleles (HLA-A1 and -A11). Another fragment was positively associated with five HLA-B series alleles (HLA-B5, -B7, -B14, -Bw16, and -Bw35) and one fragment was positively associated with alleles at two loci (HLA-B14 and -Cw5). The serologically defined allele HLA-Aw24 was associated with two polymorphic fragments, one association showing a positive correlation and the other a negative correlation. Each informative family studied thus far has shown segregation of the restriction fragment with the associated serologically defined allele. The fragments associated with serologically defined alleles occurred in the population sample studied at low or moderate frequencies. The remaining polymorphic fragments occur at high frequency, suggesting that class I genes not serologically detected show less polymorphism than serologically defined class I genes.

Alleles↗

PubMed1991

Drift, admixture, and selection in human evolution: a study with DNA polymorphisms.

Accuracy of evolutionary analysis of populations within a species requires the testing of a large number of genetic polymorphisms belonging to many loci. We report here a reconstruction of human differentiation based on 100 DNA polymorphisms tested in five populations from four continents. The results agree with earlier conclusions based on other classes of genetic markers but reveal that Europeans do not fit a simple model of independently evolving populations with equal evolutionary rates. Evolutionary models involving early admixture are compatible with the data. Taking one such model into account, we examined through simulation whether random genetic drift alone might explain the variation among gene frequencies across populations and genes. A measure of variation among populations was calculated for each polymorphism, and its distribution for the 100 polymorphisms was compared with that expected for a drift-only hypothesis. At least two-thirds of the polymorphisms appear to be selectively neutral, but there are significant deviations at the two ends of the observed distribution of the measure of variation: a slight excess of polymorphisms with low variation and a greater excess with high variation. This indicates that a few DNA polymorphisms are affected by natural selection, rarely heterotic, and more often disruptive, while most are selectively neutral.

Animals↗

PubMed1992

Mapping genes in the mouse using single-strand conformation polymorphism analysis of recombinant inbred strains and interspecific crosses.

We have utilized a PCR-based analysis of single-strand conformation polymorphisms to identify polymorphisms that can be used for mapping cloned DNA sequences in the mouse. We have found that single-strand conformation polymorphism analysis of sequences that are potentially less subject to conservation (i.e., intron and 3' untranslated regions) is a relatively efficient means of detecting polymorphisms between inbred strains. Fifty percent of the tested primer pairs were polymorphic between inbred strains and 90% were polymorphic between mouse species, which is a frequency comparable to that found for microsatellite repeat sequences. We have found that this technique can be readily used to determine the strain distribution pattern in a recombinant inbred series and is a simple and rapid means to obtain a map position for cloned sequences. When this strategy was tested on a number of previously mapped cloned genes, the strain distribution patterns obtained were consistent with that to be expected on the basis of the known map position. We also tested the utility of this approach for characterizing genes that have not been previously mapped. Dvl, the mouse homolog of the putative Drosophila dishevelled gene, and Adfp, encoding an adipocyte differentiation-related protein, were found to map to chromosome 4. These results were confirmed using single-strand conformation polymorphism analysis of an interspecific backcross.

Animals↗

PubMed2004

The enzymatic activities of the Werner syndrome protein are disabled by the amino acid polymorphism R834C.

The Werner syndrome protein, WRN, is a member of the RecQ family of DNA helicases. It possesses both 3'-->5' DNA helicase and 3'-->5' DNA exonuclease activities. Mutations in WRN are causally associated with a rare, recessive disorder, Werner syndrome (WS), distinguished by premature aging and genomic instability; all are reported to result in loss of protein expression. In addition to WS-linked mutations, single nucleotide polymorphisms, with frequencies that exceed those of WS-associated mutations, are also present in WRN. We have initiated studies to determine if six of these polymorphisms affect the enzymatic activities of WRN. We show that two common polymorphisms, F1074L and C1367R, and two infrequent polymorphisms, Q724L and S1079L, exhibit little change in activity relative to wild-type WRN; the polymorphism, T172P, shows a small but consistent reduction of activity. However, an infrequent polymorphism, R834C, located in the helicase domain dramatically reduces WRN helicase and helicase-coupled exonuclease activity. The structure of the E. coli helicase core suggests that R834 may be involved in interactions with ATP. As predicted, substitution of Arg with Cys interferes with ATP hydrolysis that is absolutely required for unwinding DNA. R834C thus represents the first missense amino acid polymorphism in WRN that nearly abolishes enzymatic activity while leaving expression largely unaffected.

Adenosine Triphosphatases↗

PubMed2006

Analysis of two polymorphisms in the promoter region of matrix metalloproteinase 1 and 3 genes in women with endometriosis.

BACKGROUND: Matrix metalloproteinases are a family of proteolytic enzymes that can degrade extracellular matrix components and have been implicated in connective tissue remodeling associated with cancer invasion and metastasis. These proteins are also involved in the invasive events underlying endometriotic lesion formation and aggressive behavior. Given the established genetic background of endometriosis, the aim of this study was to examine the potential impact of two polymorphisms in the gene promoter region of two of these enzymes, matrix metalloproteinases 1 and 3, on predisposition and severity of the disease. METHODS: Genomic DNA was obtained from 56 Italian Caucasian women with a surgical diagnosis of endometriosis and a control group of 71 age-matched Caucasian healthy female blood donors. In control women, endometriosis was ruled out by evaluation of the medical history, gynecologic examinations, and ultrasound scanning. Two polymorphisms have been specifically investigated: 1. a single insertion polymorphism (2G) in the matrix metalloproteinase-1 promoter region known to elevate transcriptional level of matrix metalloproteinase-1; and 2. a single insertion/deletion polymorphism (5A/6A) located in the promoter of the matrix metalloproteinase-3 gene with functional significance in the regulation of its expression. Genotypes were determined by PCR amplification and sequence analysis. RESULTS: Allele and genotype frequencies of both polymorphisms did not significantly differ between endometriosis and control groups. Moreover, no significant difference for both polymorphisms was observed in relation to the clinical stage and recurrence status of the disease. CONCLUSIONS: This is the first study that has evaluated the possibility that gene variants of matrix metalloproteinases might be involved in the susceptibility to endometriosis. However, these results suggest that matrix metalloproteinases 1 and 3 promoter polymorphism do not constitute an important factor for the genetic predisposition to endometriosis and its invasive behavior in the Italian population.

Adult↗