Joint Bone Spine 79 (2012) 256–261 Original article Suggestive linkage to chromosome 1q for bone mineral apparent density in Brazilian sister adolescents Romulo Maia Carlos Fonseca a , Nanci Maria de Franc ¸a a , Rinaldo Wellerson Pereira a,b,∗ a Programa de Pós-Graduac ¸ ão em Educac ¸ ão Física, Universidade Católica de Brasília, QS 07 Lote 1 EPCT, Sala G-115, 71966-700 Águas Claras - Taguatinga/DF, Brazil b Programa de Pós-Graduac ¸ ão em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, SGAN 916, Módulo B, Bloco C, Sala 220, 70.790-160 Brasília/DF, Brazil article info Article history: Accepted 6 May 2011 Available online 2 July 2011 Keywords: Bone mineral density Adolescents Interethnic admixed population Linkage Chromosome 11q abstract Objective: To investigate linkage to chromosome 1q and 11q region for lumbar spine, femoral neck and total body BMD and volumetric BMD in Brazilian sister adolescents aged 10–20-year-old and 57 mothers. Methods: We evaluated 161 sister pairs (n = 329) aged 10–20 years old and 57 of their mothers in this study. Physical traits and lifestyle factors were collected as covariates for lumbar spine (LS), femoral neck (FN) and total body (TB) BMD and bone mineral apparent density (BMAD). We selected nine microsatel- lite markers in chromosome 1q region (spanning nearly 33cM) and eight in chromosome 11q region (spanning nearly 34cM) to perform linkage analysis. Results: The highest LOD score values obtained from our data were in sister pairs LS BMAD analysis. Their values were: 1.32 (P < 0.006), 2.61 (P < 0.0002) and 2.44 (P < 0.0004) in D1S218, D1S2640 and D1S2623 markers, respectively. No significant LOD score was found with LS and FN BMD/BMAD in chromosome 11q region. Only TB BMD showed significant linkage higher than 1.0 for chromosome 11q region in the markers D11S4191 and D11S937. Discussion/Conclusions: Our results provided suggestive linkage for LS BMAD at D1S2640 marker in ado- lescent sister pairs and suggest a possible candidate gene (LHX4) related to adolescent LS BMAD in this region. These results reinforce chromosome 1q21-23 as a candidate region to harbor one or more bone formation/maintenance gene. In the other hand, it did not repeat for chromosome 11q12-13 in our population. © 2011 Société franc ¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. 1. Introduction Osteoporosis is a common disease of elderly population, which is characterized by a generalized reduction in bone mineral den- sity (BMD) and an increased risk of fracture. In Brazil, the number of deaths caused by femur fracture raised from 1304 (in 2005) to 1478 (in 2009). The Brazil’s Unified Health System (SUS) spent almost R$ 81 million (US $46 million) with old-aged people fracture treatments in 2009 [1]. However, approximately 60% of the risk of osteoporosis is connected to the amount of bone mineral acquired during childhood and adolescence [2]. BMD reaches a peak in the third or fourth decade of life, however prospective studies have shown that 90–100% of its acquisition happened by the late teen years [2,3]. Bone mass acquisition is a very complex physiological trait influenced by genetics and environmental factors like mechanical loading, nutrition, etc. [4]. The heritability of BMD is estimated to be around 80% [5], but gender, site and age specific patterns of linkage ∗ Corresponding author. Tel.: +55 61 3448 7222; fax: +55 61 3347 4797. E-mail address: rinaldo@pos.ucb.br (R.W. Pereira). make difficult a more accurate estimation [6]. In the last 2 decades, many strategies have been applied to elucidate genetics influence on BMD, as linkage mapping, gene-candidate association studies, whole genome association and more recently is proposed to apply a large scale genome sequencing [7]. The probability that a marker locus is linked to a disease or phenotype is expressed by the lod- score, which is the logarithm of the odds that loci are linked rather than unlinked [8]. In the case of sib pair studies, their phenotypic difference and the number of alleles shared identical-by-descent (IBD) should show a correlation. This correlation will be suggestive when the pointwise significance level is 7.4 × 10 -4 (LOD = 2.2) and considered significant when it is 2.2 × 10 -5 (LOD = 3,6) [9]. In other words, a LOD score of > +3.0 means that the chance for a locus and a phenotype is linked is 1.000 times higher than it is unlinked. Some studies, conducted in premenopausal women, suggest chromosome regions that can harbor genes related to bone for- mation or bone maintenance as the structural gene for osteocalcin and the interleukin-6 receptor gene for 1q chromosome region, and two known genes associated with BMD variation in chro- mosome 11q: lipoprotein receptor-related protein-5 (LRP5) which polymorphisms are associated to variation of peak bone mass in French-Canadian women [10] and volumetric BMD in children [11]; 1297-319X/$ – see front matter © 2011 Société franc ¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2011.05.007