The Amerindian's Genes in the Mexican Population are Associated with Development of Gallstone Disease

Abstract

BACKGROUND: It has been suggested that genes related to Amerindian ancestry account for the high prevalence of gallstone disease (GD) observed in Mexican-Americans. The HLA-B39 is an allele found in higher frequency in Amerindians whereas HLA-B15 is rarely found. The aim of this study was to test the hypothesis that gallstone susceptibility genes are more prevalent in Mexicans with recent Amerindian ancestry. METHODS: We carried out a prospective case-controlled study. Subjects were divided into those who had stones visible on gallbladder ultrasound (cases), and those whose ultrasounds were negative for gallstones (controls). Body mass index (BMI) was calculated, and serum lipids and lipoprotein, and glucose levels were measured. Class I HLA (HLA-B) typing was performed by PCR amplification of genomic DNA. RESULTS: Of the 1,101 subjects, 146 were classified as subjects with GD (cases) and 955 as subjects without GD (controls). Mean age of the cases was 53.5 ± 12.5 yr versus 44.78 ± 12.0 yr for the controls, p= 0.001. A family history of GD was observed in 48% of the cases versus 28.4% of the controls, p= 0.001. HLA-B39 was more frequently increased in GD subjects (0.162), compared with controls (0.063), p= 0.008. The odds ratio of having HLA-B39 was 2.8 and 95% (CI 95%= 1.3-6.3) for GD; HLA-B15 was more frequently increased in controls than in cases. CONCLUSIONS: The most prevalent HLA alleles detected in these GD cases are characteristic of Amerindian populations, supporting the role of genetics in the high prevalence of the development of GD in Mexican mestizos.