rs1044498

blog ENPP1 harbors a mutation with a derived state known to protect against obesity and type II diabetes27 that is present in 90% of non-Africans but virtually absent in Africans

[PMID 18426862] K121Q (rs1044498) The Q allele of ENPP1 K121Q is associated with hyperglycemia and insulin resistance in whites. increased fasting plasma glucose (FPG), A1C, fasting insulin, and insulin resistance by homeostasis model assessment (HOMA-IR; all P = 0.01-0.006).

[PMID 19399648] Possible role for ENPP1 polymorphism in obesity but not for INSIG2 and PLIN variants

[PMID 19656007] Genetic Variants of the ENPP1/PC-1 Gene Are Associated with Hypertriglyceridemia in Male Subjects

[PMID 20091022] The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention

[PMID 21198320] Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 K173Q Polymorphism Is Associated with Diabetic Nephropathy in the Taiwanese Population

[PMID 21282363] The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

[PMID 21565692] ENPP1/PC-1 Gene K121Q Polymorphism Is Associated with Obesity in European Adult Populations: Evidence from A Meta-Analysis Involving 24 324 Subjects

[PMID 16207325] Association of ENPP1 gene polymorphisms with hand osteoarthritis in a Chuvasha population.

[PMID 16865358] Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects.

[PMID 17065359] Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity.

[PMID 17704904] ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study.

[PMID 18184924] Association of the distal region of the ectonucleotide pyrophosphatase/phosphodiesterase 1 gene with type 2 diabetes in an African-American population enriched for nephropathy.

[PMID 18498634] The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.

[PMID 18603647] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

[PMID 18678618] Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

[PMID 18719658] Gender differences in the relationship of ENPP1/PC-1 variants to obesity in a Turkish population.

[PMID 18950909] Association of the Q121 variant of ENPP1 gene with decreased kidney function among patients with type 2 diabetes.

[PMID 19017751] The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the diabetes prevention program.

[PMID 19368707] Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study.

[PMID 19593725] Association of maternally inherited GNAS alleles with African-American male birth weight.

[PMID 19643578] Genetic risk factors for type 2 diabetes with pharmacologic intervention in African-American patients with schizophrenia or schizoaffective disorder.

[PMID 20981035] The ENPP1 K121Q polymorphism is not associated with type 2 diabetes or obesity in the Chinese Han population.

[PMID 21283750] Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans.

[PMID 22391941] Meta-analysis of association studies between five candidate genes and type 2 diabetes in Chinese Han population.

[PMID 23036011] Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases

[PMID 23111648] Evaluation of the ENPP1 and PLIN Single Nucleotide Polymorphisms With Type 2 Diabetes in a Taiwanese Population: Evidence for Replication and Gene-Gene Interaction

[PMID 22749234] Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL, PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs

[PMID 23633196] Joint effect of insulin signaling genes on insulin secretion and glucose homeostasis

[PMID 24332798] Maternal-fetal metabolic gene-gene interactions and risk of neural tube defects

[PMID 23107043] Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance.

[PMID 25794151] Association between the ENPP1 K121Q Polymorphism and Risk of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

[PMID 25463099] Joint effect of insulin signaling genes on all-cause mortality

rs1044498 is a SNP in the ENPP1 gene. It is shown to be associated with insulin resistance and type 2 diabetes (T2D) in various ethnic populations. It is also significantly associated with T2D/obesity-related metabolic traits, such as waist circumference (P = 0.002) and fasting glucose (P < 0.001) [R].

 The ''AC+CC'' genotype was a risk factor for the development of nephropathy in diabetic patients. Further, the ''AC+CC'' genotype was a genetic risk factor in obese (defined by waist circumference) diabetic patients, but not in nonobese diabetic patients [R].

The ''C'' allele increase the risk of type 2 diabetes in the Chinese Han population (OR=1.41;P = 0.003) [R]. 

Compared to the carrier of the ''AA'' genotype the likelihood of type 2 diabetes (T2D) was 2.442 for the carrier of combined ''AC+CC'' genotypes after adjustment of sex and body mass index [R].

Carriers of the ''C'' allele had a decreased risk of colorectal cancers (CRC) (OR 0.79; p≤0.05). And the strongest association was detected in the male subpopulation (OR 0.61; p=0.0015) [R].