Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations

Abstract

BackgroundThe global burden of chronic liver disease is rising. Besides environmental, behavioral, viral and metabolic factors, genetic polymorphisms in patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have been related to the development of chronic liver disease and progression towards liver cancer. Although their prevalence differs remarkably among ethnic groups, the frequency of these polymorphisms in South American populations -whose genetic background is highly admixed- has been poorly studied. Hence, the aim of this study was to characterize polymorphisms related to chronic liver disease and their association with the genetic ancestry of South American populations.ResultsDNA samples from 258 healthy unrelated male volunteers were analyzed. The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74 % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA) haplotype -associated with an increased risk of chronic liver disease and progression towards liver cancer- were significantly more frequent among samples exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %), intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008).ConclusionsThese results suggest that individuals with Native American ancestry might have a high risk of chronic liver disorders and cancer. Furthermore, these data not only support the molecular evaluation of ancestry in multi-ethnic population studies, but also suggest that the characterization of these variants in South American populations may be useful for establishing public health policies aimed at high risk ethnic communities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0255-3) contains supplementary material, which is available to authorized users.

The CYP2B6 G516T polymorphism influences CD4 + T-cell counts in HIV-positive patients receiving antiretroviral therapy in an ethnically diverse region of the Amazon

“…24 Santos et al (2009) described the participation of Europeans (60%), native Indians (28%), and Africans (12%) in the foundation of the city of Belé m. 31 Recent studies have demonstrated that the genetic influence of ethnicity or ancestry might be related to variations in the genes involved in the individual's responses to certain diseases. 25,32 Therefore, the level of ethnic diversity present in the study population may influence the frequency of the CYP2B6 G516T polymorphism compared with different ethnic groups. The frequency of the polymorphic allele previously determined for individuals in the city of Belé m who were receiving treatment for tuberculosis (0.30) is similar to the frequency found in the present study (0.36).…”

Nonalcoholic Fatty Liver Disease Risk Factors in Latin American Populations: Current Scenario and Perspectives

“…Some data from Latin America show a high prevalence of p.I148M in the general population and even higher prevalence in individuals with Native American ancestry. A preliminary study from Chile reported an allelic frequency of the high‐risk allele G of 59% in the general population, whereas in Argentina, Pontoriero et al reported in a study involving 258 healthy unrelated male volunteers that the GG genotype of PNPLA3 rs738409 was present in 63.7% of individuals with maternal and paternal Native American ancestry. It is important to consider that admixture of Native Americans, Europeans, and Africans is variable throughout Latin America, which makes the genetic makeup of each country considerably heterogeneous .…”

Spectrum of Alcoholic Liver Disease

“…15 The PNPLA3 polymorphism seems to be more prevalent in persons of native-American ancestry from South America compared with non-native South Americans; for example, those of Spanish, European, and African ancestry. 16 A high frequency of PNPLA3 variants and a strong association of these variants with increased serum alanine aminotransferase (ALT) levels has been found in indigenous Mexican and Mestizo peoples. 17 In white Europeans, the PNPLA3 polymorphism is more common in patients with ALD compared with controls and is significantly associated with the presence of steatosis, fibrosis, and cirrhosis.…”