Gender‐dependent association of the <i>GNAS1</i> T393C polymorphism with early aseptic loosening after total hip arthroplasty

Bachmann, Hagen S.; Hanenkamp, Sandra; Kornacki, B; Frey, Ulrich H.; Bau, Maja; Siffert, Winfried; Wedemeyer, Christian

doi:10.1002/jor.20699

Cited by 20 publications

(17 citation statements)

References 40 publications

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“…Interestingly, ADRB1 and ADRB2 alleles are associated with differential gender responses in blood pressure [38], and in rats these genes interact with sex hormones in a differential manner [39]. The GNAS gene was associated with different responses to hip arthroplasty [40]. While allele frequency differences between the sexes may not be frequent when they occur this may be an indicator of potential gene-gender interactions for future research.…”

Section: Discussionmentioning

confidence: 99%

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project

et al. 2010

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BackgroundThere is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined.ResultsThere were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders.ConclusionsThis represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and implementation of studies and for determining the relevance of a disease associated polymorphism for a given population.

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Section: Discussionmentioning

confidence: 99%

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project

et al. 2010

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“…This work led to some orthopaedic device manufacturers developing ''gender-specific'' total knee prostheses in an attempt to provide more options for the surgeon and patient (such as incorporating more sizes, differing aspect ratios, altered trochlear grooves, and other features). Additionally, as a greater understanding of the variability of hip and knee anatomy has been attained [2,9,40,49], implants have been redesigned with more modularity in their systems.…”

Section: Introductionmentioning

confidence: 99%

Do We Need Gender-specific Total Joint Arthroplasty?

Johnson

Costa

Mont

2011

Clinical Orthopaedics &Amp; Related Research

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Background Gender-specific differences in knee and hip anatomy have been well documented. Although it has been accepted these differences exist, there is controversy regarding if and how these differences should be addressed with gender-specific implant designs. Questions/purposes (1) What are the anatomic and morphologic differences, if any, in the knee and hip between men and women? (2) Do gender-specific TKA designs provide better clinical functioning, survivorship, and improved fit in women? (3) How have anatomic differences in the hip been addressed, if at all, by THA? Methods We conducted a systematic review of the MEDLINE database to identify all articles reviewing basic science and clinical outcomes of gender-specific total knee and total hip implants. From these, we reviewed 253 studies.Results The anatomic studies elucidated multiple differences in the anatomy of knees and hips between men and women. All reviewed studies report similar clinical function and satisfaction scores between men and women for gender-specific TKA and no improvement in these scores when comparing gender-specific TKA to unisex TKA.

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“…Indeed, we addressed these limitations in our article. 1 We are aware that multiple factors can influence the time to loosening, that is, inconvenient implants, surgical inexperience, low grade sepsis but it is also known that Il-6 is a key factor in particle induced osteolysis and might be a potential target for further investigations like we did. 2 This study is one of the first studies analyzing the impact of genetic background in relation to time to aseptic loosening.…”

Section: Replymentioning

confidence: 85%

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Bachmann

Hanenkamp

Kornacki

et al. 2010

Journal Orthopaedic Research

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ReplyWe thank Dr. Gallo, Dr. Mrazek, and Dr. Petrek for their interest in our work. We generally agree with their comments regarding its limitations. Indeed, we addressed these limitations in our article. 1 We are aware that multiple factors can influence the time to loosening, that is, inconvenient implants, surgical inexperience, low grade sepsis but it is also known that Il-6 is a key factor in particle induced osteolysis and might be a potential target for further investigations like we did. 2 This study is one of the first studies analyzing the impact of genetic background in relation to time to aseptic loosening. The results are preliminary and should be interpreted with some caution. We stated explicitly that a limited number of patients was investigated. However, we do not agree with Gallo and coworkers regarding their remarks to statistics and sample size determination. Their suggestions and the cited articles are dealing with genetic data in relation to dichotomous variables (i.e., no failure vs. failure) which would lead to contingency tables. 3,4 Our approach was the assessment of the time dependence of this failure with respect to different genotypes, which typically leads to Kaplan-Meier curves and survival analysis. 5 Our results support the concept of a role of GNAS1 genotype in aseptic loosening. Nevertheless, further independent (prospective) studies are necessary to back up the general findings and deduced hypothesis. Independent of this specific polymorphism, we believe that mapping the genetic background could lead to a better understanding of pathomechanisms and the development of individual therapeutic concepts.

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Gender‐dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty

Cited by 20 publications

References 40 publications

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project

Do We Need Gender-specific Total Joint Arthroplasty?

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