***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The genes responsible for insulin resistance are poorly defined . Plasma cell differentiation antigen ( PC-1 ) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance . We describe here a novel polymorphism in exon 4 of the PC-1 gene ( K121Q ) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese ( BMI < 30 kg/m2 ) nondiabetic ( by oral glucose tolerance test [ OGTT ] ) Caucasians from Sicily . Compared with 80 KK subjects , Q allele carriers ( n = 41 , 39 KQ and 2 QQ ) showed higher glucose and insulin levels during OGTT ( P < 0.001 by two-way analysis of variance ) and insulin resistance by euglycemic clamp ( M value = 5.25 + /- 1.38 [ n = 24 ] vs. 6.30 + /- 1.39 mg x kg(-1 ) x min(-1 ) [ n = 49 ] , P = 0.005 ) . Q carriers had higher risk of being hyperinsulinemic and insulin resistant ( odds ratio [ CI ] : 2.99 [ 1.28 - 7.0 ] , P < 0.001 ) . Insulin receptor autophosphorylation was reduced ( P < 0.01 ) in cultured skin fibroblasts from KQ versus KK subjects . Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects ( 33 + /- 16.1 vs. 17.5 + /- 15 ng/mg protein , P = 0.3 ) . These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype , and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance , a condition that predisposes to type 2 diabetes and coronary artery disease The calpain-10 gene ( CAPN10 ) on chromosome 2q37.3 was the first c and i date gene for type 2 diabetes ( T2D ) identified through a genomewide screen and positional cloning . One polymorphism ( UCSNP-43 : G-->A ) and a specific haplotype combination defined by three polymorphisms ( UCSNP-43 , -19 , and -63 ) were linked to an increased risk of T2D in several population s. To quantitatively assess the collective evidence for the effects of CAPN10 on risk of T2D , we conducted a meta- analysis of both population -based and family-based association studies . We retrieved data from the MEDLINE , PubMed , and Online Mendelian Inheritance in Man data bases , as well as from other relevant reports and abstract s published up to July 2003 . From a total of 26 studies with primary data ( 21 population -based studies : 5,013 cases and 5,876 controls ; 5 family-based studies : 487 parent-offspring trios ) , we developed a summary data base that contains variables of study design , study population /ethnicity , specific polymorphisms and haplotype combinations in CAPN10 , and diabetes-related metabolic phenotypes . For population -based studies , we used both fixed-effects and r and om-effects models to calculate the pooled odds ratio ( OR ) and 95 % confidence interval ( CI ) for the associations of CAPN10 genotypes with the risk of T2D . We also calculated weighted mean differences for the associations between CAPN10 and diabetes-related quantitative traits . Under either an additive or a dominant effect model , we found no statistically significant relation between CAPN10 genotypes in the UCSNP-43 locus and T2D risk . However , under a recessive model , individuals homozygous for the common G allele had a statistically significant 19 % higher risk of T2D than carriers of the A allele ( OR 1.19 ; 95 % CI 1.07 - 1.33 ) . The association between the 112/121 haplotype combination and T2D risk appeared to be overestimated by several initial small studies with positive findings ( OR 1.38 ; 95 % CI 1.04 - 1.84 ) . After we removed these initial studies , this association became nonsignificant ( OR 1.11 ; 95 % CI 0.91 - 1.35 ) . Moreover , we found no evidence for the associations between the UCSNP-43 G/G genotype and the 112/121 haplotype combination and metabolic phenotypes . Our meta- analysis of family-based studies showed only an overtransmission of the rare allele C in UCSNP-44 from heterozygous parents to their affected offspring with T2D . Our analysis indicates that inadequate statistical power , racial/ethnic differences in frequencies of alleles , haplotypes and haplotype combinations , potential gene-gene or gene-environment interactions , publication bias , and multiple hypothesis testing may contribute to the significant heterogeneity in previous studies of CAPN10 and T2D . Our findings also suggest that both large-scale , well- design ed association studies and functional studies are warranted to either reliably confirm or conclusively refute the initial hypothesis regarding the role of CAPN10 in T2D risk 
    Output:
    
—The ENPP1 Q121 variant increases risk of type 2 diabetes under a recessive model of inheritance in whites , an effect that appears to be modulated by BMI