Correspondence
Polymorphism of the Collagen Type Iα1 Gene and Ethnic Differences in Hip-Fracture Rates
N Engl J Med 1998; 339:351-352July 30, 1998
- Article
To the Editor:
The susceptibility to osteoporotic fracture varies markedly among ethnic groups, and the differences are partly independent of differences in bone mass. For example, hip fractures are rare in elderly black Africans and in Asians, even though bone-density values in these people are similar to those in age-matched white people.1 Genetic factors, which may include genetic differences in bone quality, are important in the pathogenesis of osteoporosis. Although the molecular mechanisms that underlie these differences are unclear, Uitterlinden et al.2 recently reported that a guanosine–thymidine substitution in a regulatory region of the collagen type Iα1 gene (COLIA1) 3 predicted osteoporotic fractures by mechanisms that were partly independent of an effect on bone mass.
We studied the relation between COLIA1 alleles and the prevalence of hip fractures in women from different countries. Data on the frequency of COLIA1 alleles were obtained from published reports4-6 or from an analysis of genomic-DNA samples obtained from 150 normal women in the Gambia and 117 normal women in northeastern China. The incidence rates for hip fracture in women were obtained from the same countries, age-standardized to the population of England and Wales with the use of 1990 census data, and plotted against the population prevalence of the COLIA1 s allele, which corresponds to the thymidine variant of the polymorphism (Figure 1Figure 1
Comparison of the Age-Adjusted Incidence of Hip Fracture and the Frequency of the COLIA1 s Allele in Women in Different Populations.). The prevalence of the s allele was low in Africa and Asia, where hip fractures are rare, and higher in white women from northern European countries where these fractures are common.Previous studies estimated that carriage of the s allele is associated with an increased relative risk of osteoporotic fracture ranging from 1.52 to 3.0.3 We estimate that population differences in the prevalence of the s allele could account for between 1.7 and 6.8 percent of the difference in hip-fracture rates between Asian and European countries. This is consistent with the view that the genetic contribution to osteoporosis is mediated by several genes, each with modest effects, rather than a few genes with large effects. These data raise the possibility that ethnic differences in the risk of hip fracture may be due in part to ethnic differences in the prevalence of COLIA1 alleles.
6 ReferencesSian Beavan, Ph.D.
Ann Prentice, Ph.D.
Bakary Dibba, M.Sc.
Medical Research Council Dunn Nutrition Unit, Cambridge CB4 1XJ, United KingdomLiya Yan
Shenyang Medical College, Shenyang 110031, People's Republic of ChinaCyrus Cooper
Medical Research Council Environmental Epidemiology Unit, Southampton SO16 6YD, United KingdomStuart H. Ralston, M.D.
University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom1
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