WNT3A gene polymorphisms are associated with bone mineral density variation in postmenopausal mestizo women of an urban Mexican population: findings of a pathway-based high-density single nucleotide screening

Abstract

Osteoporosis (OP) is a common skeletal disorder characterized by low bone mineral density (BMD) and is a common health problem in Mexico. To date, few genes affecting BMD variation in the Mexican population have been identified. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) located in genes of the Wnt pathway with BMD variation at various skeletal sites in a cohort of postmenopausal Mexican women. A total of 121 SNPs in or near 15 Wnt signaling pathway genes and 96 ancestry informative markers were genotyped in 425 postmenopausal women using the Illumina GoldenGate microarray SNP genotyping method. BMD was measured by dual-energy X-ray absorptiometry in total hip, femoral neck, Ward's triangle, and lumbar spine. Associations were tested by linear regression for quantitative traits adjusting for possible confounding factors. SNP rs752107 in WNT3Awas strongly associated with decreased total hip BMD showing the highest significance under the recessive model

Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases

“…67 Furthermore, LRP6 rs1181334 was also associated with decreased total hip BMD (P = 0.014) in 425 postmenopausal woman of an urban Mexican population. 68 These data support previously reported associations of LRP6 with BMD. 69 In the past years, it has been established that LRP6 controls osteoblast differentiation in mice models.…”

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults

“…The GoldenGate BeadArray (Illumina) was used to genotype a set of 96 AIMs distributed across the genome. These AIMs have been validated in other studies of the Mexican population to primarily distinguish between the American, European and African populations [30, 31]. …”

Genome-Wide Survey of Runs of Homozygosity Identifies Recessive Loci for Bone Mineral Density in Caucasian and Chinese Populations

“…Previous studies have identified a number of recessive genes influencing osteoporosis, including VDR, (49) LRP5 , (22) and WNT3A , (24) et al We examined associations of ROHs including these recessive genes with BMD and fractures in our study. We confirmed several recessive genes at the replication level.…”

“…Osteoporosis could be affected by recessive loci. (22–24) For instance, variation in WNT3A was strongly associated with hip BMD under the recessive model. (24) SNP rs312009 in the 5′-flanking region of LRP5 was associated with BMD under the recessive model.…”

“…(22–24) For instance, variation in WNT3A was strongly associated with hip BMD under the recessive model. (24) SNP rs312009 in the 5′-flanking region of LRP5 was associated with BMD under the recessive model. (22) A haplotype in the SRPY1 gene showed association with an increased risk for osteoporosis in the recessive genetic model.…”