Association Between Polymorphisms Of COL11A1 Gene Promoter And Adult Height In Chinese Han Population

Background Body height is a multifactorial characteristic that responds to both genetic and environmental influences. The heritability of height was about 0.80. As a quantitative traits , the inheritance pattern of stature can be expained by the combination of many gene effects. The height of an individual is the result of many growth and development processes,and great stature is not just a result of increasing bone length; tissue and organ sizes are usually also proportionately increased. Searching for height genes will help us to understand the mechanism of human growth and development processes. Normal variation of height is also associated with a range of diseases, including type 2 diabetes; cardiovascular diseases and various cancers, therefore, a better understanding of the gene variants underlying height differences might also provide novel insights into these disorders.To date,Online Mendelian Inheritance in Man(OMIM) has collected sixteen adult height susceptibility loci, 6q24(STQTL1),7q31-q36(STQTL2),12p11-q14(STQTL3),13q32-q33(STQTL4),3p26(STQTL5),Xq24(STQTL6),1p21(STQTL7),9q22(STQTL8),12q14.3(STQTL9),3q23(STQTL10),7q21-q22(STQTL11),4q28-q32(STQTL12),4p13.3(STQTL13),20q11.22(STQTL14),8q21.13(STQTL15),15q22.31(STQTL16).Tens of candidate genes has been associated with height,including ESR1, GH/IGF1,VDR,CYP19 and so on. From 2007,large-scale genome-wide association studies were used to analyze the genetic factors of body stature, there were 44 loci known to influence normal variation of height. Because of the different methods, genetic heterogeneity, gene-gene interaction, gene-enviroment influence, the results varied from different designs. In the present study, we examined genome-wide association data from 1289 individuals , two tagging SNPs in COL11A1 gene promoter , rs6692914 and rs11164719 , were associated with adult height. We confirmed the association in 1073 additional samples.Objectives To analyze the correlation between polymorphisms of COL11A1 gene promoter and adult height in Chinese Han population.Methods We examined genome-wide association data from 1289 Chinese individuals. Tagging SNPs in COL11A1 gene promoter , rs6692914 and rs11164719 , were associated with adult height (P=6.0×10-4 and P=8.1×10-4, respectively). We validated the association in the additional 1073 samples. Plink was used to calculate the linear regression P values and the estimated effect size under an additive model.Results Rs6692914 and rs11164719 were associated with adult height in Chinese Han population. The P values of rs6692914 were 6.0×10-4 and 2.0×10-3 in the preliminary screening and validation stages. and the P values of 11164719 were 8.1×10-4 and 1.0×10-3 in the two stages. The Pcombined values of this two SNPs were 1.8×10-5 and 1.9×10-5 respectively. The estimated effects of rs6692914 A allele were 1.44cm and 0.92cm in man and woman population,rs6692914 per A allele could increase 0.07 Z-score(about 0.54cm)on the average in total samples.Conclusions The polymorphisms of COL11A1 gene promoter might be associated with adult height in Chinese Han population.