Population-specific alleles: the polymorphism (k121q) of the human glycoprotein PC-1 gene is strongly associated with race but not with insulin resistance in black and white children

Morrison, John A.; Gruppo, Ralph A.; Glueck, Charles J.; Stroop, Davis; Fontaine, R; Wang, Ping; Smith, Kathleen

doi:10.1016/j.metabol.2003.10.029

Cited by 27 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The higher frequency of the Q allele observed among African descendants is in accordance with the few studies that evaluated K121Q polymorphism in different ethnic groups to date (Figure 1). In general, the Q allele is more common in populations of non-European origin (12,13). The Q allele frequency observed in African descendants in this sample (~0.50) is similar to that found in Dominican Republic type 2 DM patients (12).…”

Section: Discussionsupporting

confidence: 81%

“…Dominican Republic subjects have a higher frequency of the Q allele (>0.50) than Caucasian subjects in other countries (~0.15) (12). North American children of African ancestry have an increased prevalence of the Q allele compared to North American children of European ancestry (13). Similar findings were reported recently for African-American adults and adults of Hispanic descent (14).…”

Section: Introductionsupporting

confidence: 82%

See 1 more Smart Citation

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

Leitão

Nabinger

Krahe

et al. 2007

Braz J Med Biol Res

View full text Add to dashboard Cite

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9%, KQ = 48.2%, and QQ = 25.9%) and BD (KK = 22.0%, KQ = 53.8%, and QQ = 24.2%) compared to European descendant type 2 DM patients (KK = 62.7%, KQ = 33.3%, and QQ = 4.1%) and BD (KK = 61.0%, KQ = 35.6%, and QQ = 3.4%). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Introductionsupporting

confidence: 82%

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

Leitão

Nabinger

Krahe

et al. 2007

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…It is possible that the susceptibility induced by the polymorphism is modulated by interactions with other ethnicspecific genetic or environmental factors and that the phenotypic expression of the variant will therefore be different in various ethnic populations. In this regard it is emphasised that the frequency of the K121Q polymorphism varies considerably between different ethnic groups [24,38,42,43]. It is also recognised that many case-control studies of multifactorial diseases with inheritance as complex as that of type 2 diabetes and obesity are often statistically underpowered in order to yield conclusive results, and random spurious positive associations due to multiple testing often cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis Plasma cell membrane glycoprotein 1 (PC-1) inhibits insulin signalling by direct interaction with the insulin receptor α subunit. This inhibition is enhanced by the minor Q allele of the K121Q polymorphism (rs1044498) in the gene (ENPP1) encoding PC-1. This polymorphism has been studied in relation to insulin resistance, type 2 diabetes and obesity in several populations with conflicting results. We assessed the impact of the ENPP1 K121Q polymorphism on type 2 diabetes, obesity and quantitative metabolic traits in 7,333 Danes. Subjects and methods The K121Q polymorphism was genotyped in the population-based Inter99 study cohort (5,961 subjects) and in a group of 1,386 patients with type 2 diabetes. All subjects were Danish whites.Results No significant associations with type 2 diabetes or related quantitative metabolic traits, including measures of insulin resistance, were detected. However, a meta-analysis of the present and published studies revealed an association with type 2 diabetes (odds ratio per Q allele, 1.17 [95% CI 1.10-1.25], p=1×10 −6 ). In case-control studies comparing subjects of different BMI strata, we observed a putative association of the codon 121 QQ genotype with being overweight (BMI>25 kg/m 2 ; odds ratio 1.63 [95% CI 1.09-2.46], p=0.015), an association not observed when comparing other levels of BMI or when analysing BMI as a quantitative trait. Conclusions/interpretation In a meta-analysis, the ENPP1 codon 121 Q allele associates with type 2 diabetes. However, a similar association was not found in the present study of Danish white subjects. The effect of this variant on obesity in Danish subjects is contentious and further study is needed.

show abstract

“…Another potential source of error in association studies is population admixture (27,29). Because the frequency of ENPP1 K121Q appears variable, genetic admixture with populations at high prevalence for this polymorphism, such as those of African descent (30), may contribute to the heterogeneity of results observed in our meta-analysis (Fig. 3).…”

Section: Enpp1 (Pc-1) and Type 2 Diabetesmentioning

confidence: 98%