Παθοφυσιολογική και γενετική μελέτη της οστεοπόρωσης σε ελληνικό πληθυσμό (Doctoral thesis)

Μαρκατσέλη, Αναστασία Ε.


Οsteoporosis is a systemic skeletal disease with a strong genetic component. Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation. The main aim of the present study was to examine the influence of the A1330V and V667M polymorphisms (SNP) of LRP5 gene on lumbar spine bone mineral density (BMD) in a well-characterized cohort of peri- and postmenopausal Geeek women. In addition, we sought to determine whether serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), as well as bone metabolic markers correlate with the two SNPs. The study included 221 consecutive peri- and postmenopausal Greek women aged 40-63 yrs, who attended the osteoporosis outpatient clinic at the University Hospital of Ioannina for screening for osteoporosis. All participants underwent spinal BMD evaluation. Genotyping of A1330V and V667M SNPs was performed by real-time PCR. Levels of OPG, RANKL and bone metabolic markers were measured. The genotype frequencies of the A1330V SNP were CC (76%), CT (22.6%) and TT (1.4%) and of the V667M SNP GG (85%), GA (14.5%) and AA (0.5%). The distribution of A1330V and V667M genotypes was compatible with that of Hardy-Weinberg equilibrium (χ2=0.11, P>0.05 and χ2=0.53, P>0.05, respectively). Because of the low frequency of the TT genotype, the cohort was divided into two genotype groups regarding A1330V SNP: CC and CT/TT. Similarly, the study population was divided into two genotype groups according to the presence of V667M SNP: GG and GA/AA. Significant associations between the investigated SNPs and spinal BMD were detected. Women carrying CT/TT genotypes had lower spinal BMD than women with CC (CT/TT 0.768±0.086 g/cm2 vs CC 0.839±0.123 g/cm2; P<0.0001). Moreover, spinal BMD was lower in women with GA/AA genotypes than in women with GG (GA/AA 0.766±0.079 g/cm2 vs GG 0.829±0.123 g/cm2; P<0.0001). The associations remained significant after adjustment for age, years since menopause and body mass index. The A1330V and V667M SNPs in the LRP5 gene were in strong linkage disequilibrium. A significant interaction between the two SNP on spinal BMD was also revealed. No differences were observed in circulating OPG, RANKL levels and bone metabolic markers between the two groups of each SNP. In conclusion, the A1330V and V667M SNPs of the LRP5 gene contribute to the determination of BMD at the lumbar spine in peri- and postmenopausal Greek women.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων Σχολή Ιατρικής Τμήμα Ιατρικής Τομέας Παθολογικός Κλινική Παθολογική Πανεπιστημιακού Γενικού Νοσοκομείου Ιωαννίνων Μονάδα Ενδοκρινολογίας
Subject classification: Οστεοπόρωση
Keywords: -
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/624
Link: http://thesis.ekt.gr/thesisBookReader/id/22132#page/1/mode/2up
Appears in Collections:Διδακτορικές Διατριβές

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