SUMMARY: A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) -634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction. INTRODUCTION: A nested case-control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women. METHODS: Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology. RESULTS: Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 -634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction. CONCLUSION: Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.
SUMMARY: A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) -634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction. INTRODUCTION: A nested case-control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women. METHODS: Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology. RESULTS: Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 -634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction. CONCLUSION: Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.
Authors: Y Gong; R B Slee; N Fukai; G Rawadi; S Roman-Roman; A M Reginato; H Wang; T Cundy; F H Glorieux; D Lev; M Zacharin; K Oexle; J Marcelino; W Suwairi; S Heeger; G Sabatakos; S Apte; W N Adkins; J Allgrove; M Arslan-Kirchner; J A Batch; P Beighton; G C Black; R G Boles; L M Boon; C Borrone; H G Brunner; G F Carle; B Dallapiccola; A De Paepe; B Floege; M L Halfhide; B Hall; R C Hennekam; T Hirose; A Jans; H Jüppner; C A Kim; K Keppler-Noreuil; A Kohlschuetter; D LaCombe; M Lambert; E Lemyre; T Letteboer; L Peltonen; R S Ramesar; M Romanengo; H Somer; E Steichen-Gersdorf; B Steinmann; B Sullivan; A Superti-Furga; W Swoboda; M J van den Boogaard; W Van Hul; M Vikkula; M Votruba; B Zabel; T Garcia; R Baron; B R Olsen; M L Warman Journal: Cell Date: 2001-11-16 Impact factor: 41.582
Authors: K A Chan; S E Andrade; M Boles; D S Buist; G A Chase; J G Donahue; M J Goodman; J H Gurwitz; A Z LaCroix; R Platt Journal: Lancet Date: 2000-06-24 Impact factor: 79.321
Authors: A Viitanen; M Kärkkäinen; K Laitinen; C Lamberg-Allardt; K Kainulainen; L Räsänen; J Viikari; M J Välimäki; K Kontula Journal: Calcif Tissue Int Date: 1996-10 Impact factor: 4.333
Authors: Unnur Styrkarsdottir; Jean-Baptiste Cazier; Augustine Kong; Ottar Rolfsson; Helene Larsen; Emma Bjarnadottir; Vala D Johannsdottir; Margret S Sigurdardottir; Yu Bagger; Claus Christiansen; Inga Reynisdottir; Struan F A Grant; Kristjan Jonasson; Michael L Frigge; Jeffrey R Gulcher; Gunnar Sigurdsson; Kari Stefansson Journal: PLoS Biol Date: 2003-11-03 Impact factor: 8.029
Authors: Ahmad M Al-Bashaireh; Linda G Haddad; Michael Weaver; Debra Lynch Kelly; Xing Chengguo; Saunjoo Yoon Journal: J Environ Public Health Date: 2018-07-11
Authors: Luke V Rasmussen; Will K Thompson; Jennifer A Pacheco; Abel N Kho; David S Carrell; Jyotishman Pathak; Peggy L Peissig; Gerard Tromp; Joshua C Denny; Justin B Starren Journal: J Biomed Inform Date: 2014-06-21 Impact factor: 6.317