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lüll Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects Owen KR; Groves CJ; Hanson RL; Knowler WC; Shuldiner AR; Elbein SC; Mitchell BD; Froguel P; Ng MC; Chan JC; Jia W; Deloukas P; Hitman GA; Walker M; Frayling TM; Hattersley AT; Zeggini E; McCarthy MIDiabetes 2007[Mar]; 56 (3): 879-83Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial lipodystrophy, a syndrome of monogenic insulin resistance and diabetes. LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components. We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs capturing >90% of common variation) in several large datasets. Analysis of 2,490 U.K. diabetic case and 2,556 control subjects revealed no significant associations at either genotype or haplotype level: the minor allele at rs4641 was no more frequent in case subjects (allelic odds ratio [OR] 1.07 [95% CI 0.98-1.17], P = 0.15). In 390 U.K. trios, family-based association analyses revealed nominally significant overtransmission of the major allele at rs12063564 (P = 0.01), which was not corroborated in other samples. Finally, genotypes for 2,817 additional subjects from the International 1q Consortium revealed no consistent case-control or family-based associations with LMNA variants. Across all our data, the OR for the rs4641 minor allele approached but did not attain significance (1.07 [0.99-1.15], P = 0.08). Our data do not therefore support a major effect of LMNA variation on diabetes risk. However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001).|Adult[MESH]|Aged[MESH]|Case-Control Studies[MESH]|Diabetes Mellitus, Type 2/*genetics[MESH]|Female[MESH]|Genetic Predisposition to Disease/genetics[MESH]|Genetic Variation/*genetics[MESH]|Haplotypes[MESH]|Humans[MESH]|Lamin Type A/*genetics[MESH]|Male[MESH]|Middle Aged[MESH]|Mutation/genetics[MESH]|Odds Ratio[MESH]|Polymorphism, Single Nucleotide/genetics[MESH] |