Meta-analysis of associations between the TP53 Arg72Pro polymorphism with risk of head and neck carcinomas based on case-control studies.

Genetic factors have been shown to play a role in the development of head and neck cancers (HNCs). However, studies investigating the association between the TP53 Arg72Pro polymorphism and HNCs susceptibility have yielded conflicting results. Hence, we performed a meta-analysis of all eligible studies (up to January 1, 2012) to derive a more precise estimation of this association in order to increase understanding of the possible risk factors of HNCs. Twenty-seven case-control studies involving 3966 cases and 4387 controls were included in our analysis. Overall, no evidence of association was observed between the TP53 Arg72Pro single nucleotide polymorphism (SNP) and the risk of HNCs in any genetic model (Arg/Arg vs Pro/Pro: odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.65-1.06; Arg/Pro vs Pro/Pro: OR = 0.88, 95%CI= 0.70-1.10; Arg/Arg+Arg/Pro vs Pro/Pro: OR = 0.87, 95%CI= 0.70-1.09; Arg/Arg vs Arg/Pro+Pro/Pro: OR = 0.95, 95%CI= 0.82-1.11). Nevertheless, the TP53 Arg72Pro polymorphism shows diverse effects across different subtypes of HNCs. For example, there was a lack of association of this polymorphism with oral cavity cancer, whereas a significant association with nasopharyngeal cancer was observed. Results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism might have different effects on the risk of various subtypes of HNCs.

No evidence of association of the osteocalcin gene HindIII polymorphism with bone mineral density in Chinese women.

Osteoporosis is a major health problem, mainly characterized by low bone mineral density (BMD). Osteocalcin (also known as BGP, for bone Gla protein) is a significant biomarker of bone turnover and thus the BGP gene has been considered as an important candidate gene for osteoporosis. A few studies on the relationship between variants of the BGP gene and BMD variation, via traditional association and/or linkage methods, have yielded conflicting results. In the present study, we simultaneously tested linkage and/or association of the BGP HindIII polymorphism with BMD in a large cohort of pre-menopausal Chinese women. A total of 1,263 subjects from 402 Chinese nuclear families were examined. Each family consists of both parents and at least one daughter aged between 20-45 years. BMDs at the lumbar spine and hip were measured by dual-energy X-ray absorptiometry (DXA). Using the QTDT (quantitative transmission disequilibrium test) program, we did not detect significant evidence of linkage or association between the BGP HindIII polymorphisms and the BMD variation at any skeletal site. Our data do not support the BGP gene having a major effect on BMD variation in pre-menopausal Chinese women.

No evidence for linkage and/or association of human alpha2-HS glycoprotein gene with bone mineral density variation in Chinese nuclear families.

Osteoporosis is an important health problem in the world. Alpha2-HS glycoprotein (AHSG) is involved in bone formation and metabolism and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of the AHSG gene with the variation of bone mineral density (BMD), an important risk factor for osteoporosis. A sample of 1,260 subjects from 401 Chinese nuclear families (including both parents and their daughters) were studied. The daughters' ages ranged from 20 to 45 years. All the subjects were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) at polymorphic Sac I site inside the exon 7 of the AHSG gene. This polymorphism involves a nucleotide substitution of C to G at the middle nucleotide of the codon at amino acid position 238, resulting in the replacement of threonine (ACC) with serine (AGC). BMD was measured at the lumbar spine and hip region by dual-energy X-ray absorptiometry (DXA). Using the QTDT (quantitative trait transmission disequilibrium test), we found no significant results for association or linkage between the AHSG gene and BMD variation at the spine or hip. Our data provided no evidence to support the AHSG gene as a quantitative trait locus (QTL) for the BMD variation in a Chinese population.

Differentiation of Caucasians and Chinese at bone mass candidate genes: implication for ethnic difference of bone mass.

Bone mineral density (BMD) is an important risk factor for osteoporosis and has strong genetic determination. While average BMD differs among major ethnic groups, several important candidate genes have been shown to underlie BMD variation within populations of the same ethnicity. To investigate whether important candidate genes may contribute to ethnic differences in BMD, we studied the degree of genetic differentiation among several important candidate genes between two major ethnic groups: Caucasians and Chinese. The genetic variability of these two populations (1131 randomly selected individuals) was studied at six restriction sites exhibiting polymorphisms of five important candidate genes for BMD: the BsaHI polymorphism of the calcium-sensing receptor (CASR) gene, the SacI polymorphism of the alpha2HS-glycoprotein (AHSG) gene, the PvuII and XbaI polymorphisms of the estrogen receptor alpha (ESR1) gene, the ApaI polymorphism of the vitamin D receptor (VDR) gene, and the BstBI polymorphism of the parathyroid hormone (PTH) gene. The two ethnic groups showed significant allelic and genotypic differentiation of all the polymorphisms studied. The mean FST was 0.103, which significantly differed from zero (P < 0.01). The Chinese population had lower mean heterozygosity (0.331) than the Caucasian one (0.444); the CASR-BsaHI and PTH-BstBI polymorphisms contributed most significantly to this difference. Analysis of the intra- and inter-population variability suggests that various types of natural selection may affect the observed patterns of variation at some loci. If some of the candidate genes we studied indeed underlie variation in BMD, their population differentiation revealed here between ethnic groups may contribute to understanding ethnic difference in BMD.