title: A susceptible haplotype within APOE gene influences BMD and intensifies the osteoporosis risk in postmenopausal women of Northwest India.
abstract: BACKGROUND
  The association of apolipoprotein E (APOE) genotypes with bone mineral density (BMD) and risk of osteoporosis have remained unclear. The influence of APOE gene polymorphisms on BMD as genetic mediators of osteoporosis risk needs to be explored in Indian postmenopausal females where this disease is rising rampantly.
  
  
  RESULTS
  The present study investigated the role and relevance of four pertinent APOE single nucleotide polymorphisms: 5'UTR G/C (rs440446), Int2 G/A (rs769450), Exon4 T/C (rs429358), Exon4C/T (rs7412) in DEXA verified 133 osteoporotic, 57 osteopenic and 83 normal postmenopausal females of India, who were not taking hormone replacement therapy. Minor allele frequencies of rs440446 and rs429358 were higher in osteoporotic females (0.31, 0.18) than osteopenic (0.29, 0.15) and females having normal bone mass (0.16, 0.07). Disease association analysis revealed a susceptibility haplotype CGTC (in order of rs440446, rs769450, rs429358, rs7412) and the carriers of this haplotype has higher risk of osteopenia (OR 3.53, 95% CI 1.21-11.0, P=0.017) and osteoporosis (OR 3.61, 95% CI 1.53-9.48, P=0.002) after adjusting the confounding effect of age, BMI and years since menopause. Females who possess either one copy or two copies of the haplotype have lesser BMD values of lumbar spine (0.88 and 0.85 g/cm(2)) and femoral neck (0.84 and 0.82 g/cm(2)) than those females who possess zero copy (0.9 and 0.87 g/cm(2), respectively).
  
  
  CONCLUSIONS
  The present study exposed a susceptibility haplotype CGTC, within APOE gene, which was found to be associated with BMD and risk of osteopenia and osteoporosis in postmenopausal females of India.
authors.affiliation: Department of Human Biology, Punjabi University, Patiala, Punjab, India. singh_m12@rediffmail.com
authors.forename: Monica
authors.initials: M
authors.lastname: Singh
authors.forename: Puneetpal
authors.initials: P
authors.lastname: Singh
authors.forename: Surinder
authors.initials: S
authors.lastname: Singh
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Juneja
authors.forename: Taranpal
authors.initials: T
authors.lastname: Kaur
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017697:Premenopause / Q000235:genetics*; D012307:Risk Factors; D016387:Women's Health
chemical_list: D001057:Apolipoproteins E