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PubMed2006

A gene-to-gene interaction between aromatase and estrogen receptors influences bone mineral density.

OBJECTIVE: The aromatization of androgenic precursors is the main source of estrogens in postmenopausal women. We tested the hypothesis that allelic variants of the genes coding for aromatase and estrogen receptors (ER) could interact to determine the estrogenic signals on the bone tissue and, consequently, bone mineral density (BMD). DESIGN: Cross-sectional study including 331 postmenopausal women. METHODS: BMD was measured by dual energy x-ray absorptiometry. A CG polymorphism of the aromatase gene as well as three polymorphisms of ERalpha (a TA repeat in the promoter region, a C T single nucleotide polymorphism (SNP) in intron 1 and an AG SNP in exon 8) and a CA repeat polymorphism of ERbeta were studied. RESULTS: Age, body weight and the aromatase genotype were associated with BMD. Allelic variants of ERbeta and the exon 8 of ERalpha did not show a significant association with BMD. The polymorphisms located on the promoter and intron 1 of ERalpha interacted strongly with aromatase. Thus, in women TT homozygous for the ERalpha gene, there was a marked influence of aromatase genotypes on BMD: spine BMD was 0.724 +/- 0.027 g/cm2 in women with CC aromatase alleles and 0.926 +/- 0.032 g/cm2 in those with GG alleles (P < 0.001). Hip BMD in women with CC and GG aromatase genotypes was 0.722 +/- 0.020 and 0.842 +/- 0.026 g/cm2 respectively (P = 0.002). On the contrary, there were no aromatase-related differences in BMD in women with CT/CC alleles of ERalpha. Similarly, aromatase-related differences in BMD were found in women with short alleles at the promoter region of ERalpha, but not in those with long alleles. Both ERalpha polymorphisms were in strong linkage disequilibrium (P < 0.001). CONCLUSION: These results suggest that the interaction between polymorphisms of genes involved in estrogen synthesis and estrogen signaling exerts an important influence on BMD in postmenopausal women, thus helping to explain, in part, its heritable component. Nevertheless, further studies are warranted to confirm this gene-to-gene interaction in other populations.

Absorptiometry, Photon↗
PubMed1998

Sequence analysis of thyroid transcription factor-1 gene reveals absence of mutations in patients with thyroid dysgenesis but presence of polymorphisms in the 5' flanking region and intron.

Congenital hypothyroidism is caused by several mechanisms. The most common cause worldwide is iodine deficiency, but in iodine-sufficient regions thyroid dysgenesis is the most common cause of congenital hypothyroidism. In the present study we analyzed the thyroid transcription factor-1 (TTF-1) gene in patients with congenital hypothyroidism due to thyroid dysgenesis: three patients with athyrosis, five with ectopy, and one with hypoplasia. Genomic DNA was isolated from peripheral leukocytes, and the TTF-1 gene, including a 5' flanking region, two exons and one intron was amplified by polymerase chain reaction (PCR) with 4 pairs of primers. The PCR products were directly sequenced by the Dye Terminator Cycle Sequencing method. We could not find any mutations specific for the thyroid dysgenesis in the 5' flanking region, two exons and one intron in the TTF-1 gene, but two heterozygous nucleotide substitutions were detected in the intron: a G to A transition at nucleotide 469 (G469A) and a C to A transversion at nucleotide 866 (C866A). The same nucleotide changes were detected in some normal subjects. Allelic frequencies of the polymorphisms G469A and C866A were 23% and 10%, respectively. Another normal polymorphism in the 5' flanking region was a G to T transversion at nucleotide -845 from the transcription start site (G-845T). The allelic frequency of the polymorphism G-845T was 28%. We also found 12 polymorphisms in the 5' flanking region, two in the intron and one in the 3' untranslated region. These polymorphisms were detected in 100% chromosomes. These results suggest that congenital hypothyroidism associated with thyroid dysgenesis is unlikely to be caused by mutations in the TTF-1 gene in which, however, were detected normal polymorphisms in the 5' flanking region, intron and 3' untranslated region.

Adolescent↗
PubMed1997

Factor VIII and IX gene polymorphisms and carrier analysis in Indian population.

The efficacy of the three common intra- and extragenic polymorphic sites of the factor VIII and IX genes has been examined in the Indian population, with an aim to develop a strategy that would be accurate and informative, yet economical. The approach for hemophilia A carrier detection includes tests for BclI, XbaI, and TaqI polymorphic sites for introns 18 and 22 and the extragenic locus St 14, respectively, whereas for hemophilia B, tests include detection of TaqI, DdeI, and HhaI polymorphic sites for introns 4 and 1, and the 3' flanking region of the factor IX gene, respectively. In hemophilia A, the cumulative efficiency of these three polymorphisms has been found to be 100%, since all 37 tested families were informative for at least one of these three polymorphisms. It is of interest to note that a case of recombination between St 14 and the factor VIII gene was also observed. Of the 47 unrelated X chromosomes examined (normal = 10, factor VIII:C deficiency = 37), heterozygosity for BclI, XbaI, and St 14 was found to be 47%, 36%, and 86%, respectively, in the factor VIII gene. However, when 37 unrelated X chromosomes (normal = 10, factor IX:C = 27) were analyzed for polymorphism with TaqI, DdeI, and HhaI, it was found that the polymorphism detection rate was only 18% for the TaqI site but 45% each for the DdeI and HhaI sites, in the factor IX gene. This indicates a low effectiveness of the TaqI restriction site in carrier analysis of hemophilia B families in our population.

Alleles↗
PubMed2004

Study of association between alpha-synuclein gene polymorphism and methamphetamine psychosis/dependence.

Methamphetamine (MAP) dissipates proton gradients across the membranes of synaptic vesicles, enhances cytoplasmic dopamine (DA) concentrations, and causes calcium-independent, nonvesicular DA release into synapses. MAP is taken into the cytosol by the dopamine transporter (DAT) on the synaptic terminals of DA neurons, and endogenous DA is concurrently released through the transporter by carrier exchange mechanisms, resulting in a robust increase in DA concentration in the synaptic clefts. The enhanced DA release through DAT by MAP is the main mechanism for the reinforcing effects of MAP. The complexes of alpha-synuclein and DAT facilitate membrane clustering of the DAT, thereby accelerating DA uptake in vitro. alpha-Synuclein has been shown to be overexpressed in the midbrain DA neurons of chronic cocaine abusers. The present study was performed to study the association between the alpha-synuclein gene polymorphisms and MAP psychosis/dependence in Japanese population. Since the T10A7 polymorphic site at the 5' end of the noncoding exon 1' in the alpha-synuclein gene is highly polymorphic, we analyzed the noncoding exon 1' and intron 1, including this polymorphic site by sequencing. We confirmed four single nucleotide polymorphisms (SNPs) within 1.38 kbp of the T10A7 polymorphic site. No significant difference was found in genotype or allele frequencies in the T10A7 polymorphic site between MAP psychotic/dependent and control subjects. We found significant association between three SNPs in the vicinity of this polymorphic site in intron 1 and MAP psychosis/dependence in female subjects, but not in males. These results suggest an association of the alpha-synuclein gene polymorphisms with MAP psychosis/dependence in our female subjects. Further analyses are necessary to clarify the gender difference, by using a larger sample size and/or different ethnic groups, as well as functional variations in the alpha-synuclein gene.

Adult↗
PubMed2002

No association between the serotonergic polymorphisms and incidence of nausea induced by fluvoxamine treatment.

We investigated the association between serotonergic polymorphisms and incidence of nausea, which is the most frequent side-effect of selective serotonin reuptake inhibiters (SSRIs), in 66 patients treated with fluvoxamine in a protocolized-dosing method. We focused on three polymorphisms of serotonin (5-HT) neuronal systems such as 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeat (VNTR) polymorphism in the second intron of the 5-HTT gene (STin2) and tryptophan hydroxylase (TPH) gene polymorphism in intron 7 (TPH-A218C), which have been reported to possess positive association with treatment response to SSRIs. In addition to this, the relationship between development of nausea and treatment response was also analyzed. Results suggested that these three polymorphisms did not affect the development of fluvoxamine-induced nausea, and that incidence of nausea was not a phenomenon that predicts the treatment response to fluvoxamine.

Adult↗
PubMed1992

An A gamma globin promoter (four base-pair deletion) mutant shows linked polymorphic changes throughout the A gamma gene.

The A gamma fetal globin genes from a large Australian kindred with nondeletional A gamma hereditary persistence of fetal hemoglobin (HPFH) were cloned and sequenced. The -198 T----C mutation (British type HPFH) was demonstrated upstream of the A gamma gene on one allele. On the other allele, a 4-deletion was identified -222 to -225 bp upstream from the cap site. The 4-bp deletion allele was associated with a number of variations in the A gamma gene sequence: anA gamma T transition, in the second exon (T----C at +402 relative to the cap site); a HindIII polymorphism in the second intron; and a G gamma-like sequence in the 3' untranslated region (TCAC in place of CTCT, creating a SacI site). An association between the -222 to -225 deletion, the A gamma T polymorphism, and the second intron HindIII polymorphism has previously been reported. In addition, linkage of the HindIII polymorphism with the G gamma-like sequence in the 3' untranslated region of A gamma has also been described. The case described here is unique, with all four changes present in the one A gamma gene. It is also noteworthy because there is simultaneous occurrence of high (HPFH) and low (-222 to -225 deletion) expression mutants in the same patient. Despite the presence of the 4-bp deletion, the resulting hematological phenotype remained that of HPFH. When the 4-bp deletion promoter was studied in a K562-cell transient expression assay, there was found to be no statistically significant reduction in activity compared to the control A gamma promoter. The possible reasons for the observed differences between the in vivo and in vitro activity of this mutation are discussed.

Alleles↗
PubMed2004

Association between smoking habits and tryptophan hydroxylase gene C218A polymorphism among the Japanese population.

BACKGROUND: Genetic polymorphisms have proposed a new insight in smoking behavior. Genes in serotonin system are one of the candidates because of serotonin's role in mood regulation. A polymorphism C218A in intron 7 of the tryptophan hydroxylase (TPH) gene has been hypothesized in relation to smoking predisposition. METHODS: We examined the association on two Japanese populations: one was from the first-visit outpatients of Aichi Cancer Center Hospital during 3-month period between April and June, 2001 (N=591), and the second was from the examinees who attended a health checkup program supported by the Nagoya municipal government in 2000 (N=446). Written documents on informed consent were obtained and lifestyle questionnaires were recorded. TPH C218A genotypes were determined by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. RESULTS: The frequencies of the C- and A-allele were 52% and 48%, respectively, which was in Hardy-Weinberg equilibrium. As for current smoking status, no associations were statistically observed. It was, however, indicated that smokers with A/A genotype started smoking earlier in their life. Among male health examinees, mean ages at starting smoking were 18.7 (A/A), 19.9 (C/A), and 22.4 years (C/C), (P<0.01). Also, on the Aichi Cancer Center Hospital subjects aged 60 and older, mean ages were 19.0 (A/A), 20.2 (C/A), and 20.3 years (C/C) for males and 22.3 (A/A), 31.0 (C/A), and 33.0 years (C/C) for females (P<0.05). CONCLUSIONS: The present study demonstrated that the TPH C218A polymorphism in intron 7 had no association with current smoking status in Japanese population. The hypothesis of early smoking initiation of A/A genotype was partially in agreement.

Adolescent↗
PubMed2007

Rabbit oviductal glycoprotein 1 gene: genomic organization polymorphism analysis and mRNA expression.

The OVGP1 is an oviductal glycoprotein that has positive effects on fertilization and early embryo development. We have amplified and sequenced the rabbit OVGP1 gene, which spans 13 kb and it is formed by 11 exons and 10 introns. To find polymorphisms, a region encompassing the promoter to intron 1 has been sequenced in 22 rabbits of the H, V, R, and A Spanish lines. We have identified five SNPs and one triallelic microsatellite in the promoter region, and three SNPs and one dinucleotide INDEL in intron 1. The 10 polymorphic sites cosegregate forming two haplotypes. The allelic frequencies of the microsatellite have been analyzed in 98 rabbits belonging to the four lines and the three alleles were found in all the lines. The relative quantification of the OVGP1 mRNA in liver, kidneys, lungs, skeletal muscle, ovary, uterus, and oviduct reveals that the OVGP1 expression in the oviduct is 5,500 higher than in the uterus or ovary, whereas a low level of basal expression is detected in non-reproductive tissues. We have also compared the mRNA expression between samples of oviducts taken from non-mated rabbit and samples of oviducts at different stages of the early pregnancy, but no significant differences were found.

Animals↗
PubMed2003

Fanconi anemia in Tunisia: high prevalence of group A and identification of new FANCA mutations.

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia. Fanconi anemia is genetically heterogeneous, with at least eight distinct complementation groups of FA (A, B, C, D1, D2, E, F, and G) having been defined by somatic cell fusion studies. Six genes (FANCA, FANCC, FANCD2, FANCE, FANCG, and FANCF) have been cloned. Mutations of the seventh Fanconi anemia gene, BRCA2, have been shown to lead to FAD1 and probably FAB groups. In order to characterize the molecular defects underlying FA in Tunisia, 39 families were genotyped with microsatellite markers linked to known FA gene. Haplotype analysis and homozygosity mapping assigned 43 patients belonging to 34 families to the FAA group, whereas one family was probably not linked to the FANCA gene or to any known FA genes. For patients belonging to the FAA group, screening for mutations revealed four novel mutations: two small homozygous deletions 1693delT and 1751-1754del, which occurred in exon 17 and exon 19, respectively, and two transitions, viz., 513G-->A in exon 5 and A-->G at position 166 (IVS24+166A-->G) of intron 24. Two new polymorphisms were also identified in intron 24 (IVS24-5G/A and IVS24-6C/G).

Alleles↗
PubMed2005

Polymorphisms in the serotonin transporter gene and their relationship to two temperamental traits measured by the formal characteristics of behavior-temperament inventory: activity and emotional reactivity.

Results obtained in earlier studies indicate that 5-HTT gene polymorphisms may have a certain impact on individual differences with respect to temperamental traits. The aim of our study was to determine whether the occurrence of various alleles of the serotonin transporter gene is related to the variability of two temperamental traits postulated in the Regulative Theory of Temperament (RTT)--activity and emotional reactivity. We have demonstrated that the 5-HTTLPR polymorphism is associated with one of the RTT temperamental traits--activity. Neither the relationship between the regulatory region polymorphism and emotional reactivity nor the association between the intron 2 VNTR polymorphism and the temperamental traits under study has been confirmed.

Adolescent↗
PubMed1997

Possible association of catecholamine turnover with the polymorphic (TCAT)n repeat in the first intron of the human tyrosine hydroxylase gene.

Five allelic fragments were typed by a PCR-based process with a pair of primers specific for the polymorphic sequence due to (TCAT)n tetranucleotide repeat, a microsatellite repeat, in the first intron of the human tyrosine hydroxylase gene, i.e. A1, A2, A3, A4 and A5. Comparisons of some neurochemical parameters of the catecholamine pathway were then made between the unrelated individuals genotypically classified into six subgroups, five homozygotic and one heterozygotic. Among the six subgroups, the individuals with the A2/A2 genotype had the highest levels of serum noradrenaline and those with the A4/A4 genotype had the lowest, and the individuals with the A1/A1 genotype had the highest levels of serum homovanillic acid. These findings suggest that polymorphism of the (TCAT)n repeat in the first intron of the human tyrosine hydroxylase gene may be associated with catecholamine turnover. Possibly, the two alleles, A2 and A4, may be related to the high and low excitabilities of the noradrenergic nerves, respectively, and the allele, A1, may be associated with the up-regulation of dopamine turnover.

Adult↗
PubMed2002

Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism.

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an oxo-reductase (E to F) expressed in several glucocorticoid target tissues, including liver and adipose tissue, where it facilitates glucocorticoid-induced gluconeogenesis and adipocyte differentiation, respectively. We have isolated a full-length HSD11B1 genomic clone; the gene is more than 30 kb in length, not 9 kb in length as previously reported, principally due to a large intron 4. Two polymorphic (CA)(n) repeats have been characterized within intron 4: a CA(19) repeat 2.7 kb 3' of exon 4 and a CA(15) repeat 3 kb 5' of exon 5. The microsatellites, CA(19) and CA(15), were PCR amplified using fluorescent primers and were genotyped on an ABI 377 DNA sequencer from DNA of 413 normal individuals enrolled in the MONICA study of cardiovascular risk factors and 557 Danish men (ADIGEN study), of whom 234 were obese [body mass index (BMI), >/=31 kg/m(2) ] at draft board examination and 323 were randomly selected controls from the draftee population with BMI below 31 kg/m(2) (mean +/- SE, 21.7 +/- 0.41). Genotypic data from the normal MONICA cohort was compared with gender, 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio, and waist to hip (W:H) ratio. When analyzed by allele length (0, 1, or 2 short alleles) for the CA(19) marker, there was a trend toward a higher 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio (P = 0.058) and an increased W:H ratio (2 vs. 0.1 short; P(c) = 0.10) with overrepresentation of short alleles. The opposite was true for the CA(15) locus, with longer alleles at this locus predicting increased 11beta-HSD1 activity, particularly in females. Genotypic data from the ADIGEN case-control population was compared with clinical markers of obesity such as BMI and W:H ratio. There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2006

[Analysis of X ba I polymorphism of FVIII gene and its application on prenatal diagnosis for hemophilia A].

OBJECTIVE: To establish the linkage methods of X ba I polymorphisms specific for FVIII gene intron 22, and to find a rapid and simple system for haemophilia A (HA) carrier detection and prenatal diagnosis. METHODS: A long PCR to amplify FVIII gene intron 22 followed by X ba I digestion was used to assay the gene rate and heterozygosity rate of 206 unrelated people. Detection of intron 22 inversion by long distance PCR (LD-PCR) and XbaI, BclI, Hind III, DXS52, STR polymorphism within intron 13 and 22 by hereditary linkage analysis were assays in 20 HA pedigrees. RESULTS: The gene rate and polymorphism information contents of 206 people were 0.5475 and 0.4955 respectively, 7 of 20 HA families were diagnosed as intron 22 inversion, 6 of 13 non-inversion HA families were diagnosed by X ba I linkage analysis, 8 of 13 non-inversion HA families were diagnosed by two or more linkage analysis. CONCLUSIONS: The improved X ba I linkage analysis is a specific and useful molecular diagnosis marker. LD-PCR and five-linkage analysis can be used in prenatal HA gene diagnosis.

Factor VIII↗
PubMed2004

Marked phenotypic variability in progressive diaphyseal dysplasia (Camurati-Engelmann disease): report of a four-generation pedigree, identification of a mutation in TGFB1, and review.

Progressive diaphyseal dysplasia (PDD) (Camurati-Engelmann disease) is an autosomal dominant craniotubular dysplasia characterized by hyperostosis and sclerosis of the diaphyses of the long bones and the skull. Mutations in transforming growth factor beta-1 (TGFB1) were recently found in patients with PDD. We report on a four-generation pedigree with seven individuals affected by PDD, linkage and mutational analysis results, and review the literature. This pedigree demonstrates the autosomal dominant inheritance pattern, remarkable variation in expressivity, and reduced penetrance. The most severely affected individual had progression of mild skull hyperostosis to severe skull thickening and cranial nerve compression over 30 years. His carrier father remained asymptomatic into his ninth decade and had no radiographic hyperostosis or sclerosis of the bones. Symptomatic relatives presented with lower limb pain and weakness. They were initially diagnosed with a variety of other conditions. Two of the symptomatic individuals were treated successfully with prednisone. We genotyped 7 markers from chromosome region 19q13.1-13.3 in 15 relatives and confirmed linkage to this region in this family. We screened the TGFB1 gene for mutations and identified a missense mutation resulting in an R218H substitution in the affected individuals, the asymptomatic obligate carrier, and another unaffected relative. We genotyped the family for seven known TGFB1 polymorphisms and a novel TAAA tetranucleotide repeat in intron 1. These polymorphisms did not appear to account for the variability in disease severity in this family. Our review illustrates how the disorder can significantly compromise health. Cranial involvement, which occurs in 61% of patients, can be severe, entrapping cranial nerves or causing increased intracranial pressure. Therapy with corticosteroids should be attempted in all symptomatic patients.

Adrenal Cortex Hormones↗
PubMed2005

Polymorphisms in DNA repair genes and epithelial ovarian cancer risk.

DNA repair gene polymorphisms and mutations are known to influence cancer risk. We studied whether polymorphisms in DNA double strand break (DSB) repair genes are associated with epithelial ovarian cancer (EOC) risk. Up to 1,600 cases and 4,241 controls from 4 separate genetic association studies from 3 countries were genotyped for 13 single nucleotide polymorphisms (SNP) in 6 genes (BRCA1, NBS1, RAD51, RAD52, XRCC2 and XRCC3) involved in homologous recombination of DNA double strand breaks. Genotype specific risks were estimated as odds ratios (OR) by unconditional logistic regression. No association was detected between EOC risk and BRCA1 Q356R, BRCA1 P871L, RAD51 g135c, RAD51 g172t, RAD52 c2259t, NBS1 L34L, NBS1 E185Q, NBS1 A399A, NBS1 P672P, XRCC2 g4324c, XRCC2 c41657t and XRCC3 T241M. The XRCC2 R188H polymorphism was associated with a modest reduction in EOC risk: OR for heterozygotes was 0.8 (95% confidence interval [CI] = 0.7-1.0) and for rare homozygotes 0.3 (0.1-0.9). The XRCC3 a4541g polymorphism, situated in the 5'UTR, and the intronic XRCC3 a17893g polymorphism were not associated with EOC risk in general, but when the serous EOC subset only was analysed, the OR for heterozygotes for a4541g was 1.0 (0.9-1.2) and for the rare homozygotes 0.5 (0.3-0.9). For the XRCC3 a17893g polymorphism, the OR for the heterozygotes and the rare homozygotes were 0.8 (0.7-0.9) and 0.9 (0.7-1.2), respectively. In our study, some polymorphisms in XRCC2 and XRCC3 genes were associated with EOC risk. Further research on the role of these genes on epithelial ovarian cancer is warranted.

Adult↗
PubMed1999

Vitamin D binding protein gene in male osteoporosis: association of plasma DBP and bone mineral density with (TAAA)(n)-Alu polymorphism in DBP.

Vitamin D binding protein (DBP) is a major carrier protein for the vitamin D metabolites, but may also play an important role in osteoclast differentiation. Polymorphisms of the DBP gene have been reported, including (TAAA)(n)-Alu repeat polymorphisms downstream of intron 8. We have examined the relationship between polymorphisms of the DBP gene and bone mineral density (BMD) and vertebral fractures in a group of 26 men with vertebral fractures but no underlying secondary cause of osteoporosis (median age 64, ages 27-72 years) and 21 male control subjects (median age 65, ages 40-77 years). There was no apparent effect of DBP phenotype on BMD, but there was a relationship between certain genotypes of (TAAA)(n)-Alu repeats and reduced BMD and vertebral fracture. Lumbar spine and femoral neck BMD were significantly lower in men with 10/8 genotype than 10/10 genotype (P < 0.05). Furthermore, the predominant genotype in men with vertebral fractures was 10/8, whereas the most common genotype in control subjects was 10/10 (odds ratio 56; 95% confidence interval 7-445). Plasma DBP was higher in men with 10/8 genotype than those with 10/10 genotype (P < 0.05), and patients with vertebral fractures were found to have higher levels than control subjects (P < 0.0005). Although our study is small because of the relative rarity of idiopathic osteoporosis in men, the results suggest that (TAAA)(n)-Alu polymorphism may have an important effect on plasma levels of DBP, bone density and fracture risk in men.

Adult↗